Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or ...Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.展开更多
Background Hyperhomocysteinemia （HHcy）-mediated dysfunction of endothelial NO system is an important mechanism for atherosclerotic pathogenesis. Dimethylarginine dimethylaminohydrolase （DDAH） is the key enzyme for...Background Hyperhomocysteinemia （HHcy）-mediated dysfunction of endothelial NO system is an important mechanism for atherosclerotic pathogenesis. Dimethylarginine dimethylaminohydrolase （DDAH） is the key enzyme for degrading asymmetric dimethylarginine （ADMA）, which is an endogenous inhibitor of endothelial nitric oxide （NO） synthase （eNOS）. This study was designed to investigate whether the dysfunction of endothelial NO system originates from HHcy-mediated aberrant methylation modification in promotor region of DDAH2 gene. Methods Human umbilical vein endothelial cells （HUVECs） were cultured to the third generation and treated with homocysteine （Hcy） at different concentrations （0, 10, 30, 100, and 300 μmol/L） for 72 hours. The methylation pattern in promoter region CpG island of DDAH2 gene was analyzed by nested methylation-specific PCR （nMSP）. The mRNA expression of eNOS gene and DDAH2 gene was detected by semi-quantitative RT-PCR. The activity of DDAH2 and eNOS in cells, and the concentrations of ADMA and NO in culture medium were assayed respectively. Results Mild increased concentration of Hcy （10 and 30 μmol/L） induced hypomethylation, while high concentration of Hcy （100 and 300 μmol/L） induced hypermethylation in the promoter CpG island of DDAH2 gene. The mRNA expression of DDAH2 increased in mild enhanced concentration of Hcy, and decreased in high concentration of Hcy correspondingly. The inhibition of DDAH2 activity, the increase of ADMA concentration, the reduction of eNOS activity and the decrease of NO production were all consistently relevant to the alteration of Hcy concentration. Conclusion The increased concentration of Hcy induced aberrant methylation pattern in promotor region of DDAH2 gene and the successive alterations in DDAH/ADMA/NOS/NO pathway, which showed highly relevant and dose-effect relationship. The results suggested that the dysfunction of endothelial NO system induced by HHcy could be partially originated from Hcy-mediated aberrant m展开更多
This review describes the recent developments in the pathobiology of endothelial dysfunction(ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED ...This review describes the recent developments in the pathobiology of endothelial dysfunction(ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. EDcharacterised by an impaired bioactivity of nitric oxide(NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase(e NOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of e NOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases.展开更多
Background Endothelial cell senescence is accelerated under high glucose condition, which may contribute to the vascular complications in the diabetics, tt has been proved that aspirin has multiple cytoprotective effe...Background Endothelial cell senescence is accelerated under high glucose condition, which may contribute to the vascular complications in the diabetics, tt has been proved that aspirin has multiple cytoprotective effects. This study aimed to investigate the effect of aspirin on high glucose-induced endothelial cell senescence and its possible mechanism. Methods Human umbilical venous endothelial cells were cultured in Dulbecco＇s modified Eagle＇s medium （DMEM） with different treatments including the normal glucose （5.5 mmol/L）, high glucose （33 mmol/L） and aspirin （0.01-1.00 mmol/L） with high glucose. And 300 umol/L L-NAME was added to the culture medium when needed. After 48 hours, SA-13-gal staining was used to evaluate the senescence. Total nitric oxide （NO） production and NO synthase （NOS） activity were measured using Griess reaction and molecular probes of 3-amino-4-aminomethyl-2＇, 7＇- difluorescein, diacetate. The level of intracellular reactive oxygen species was monitored by flow cytometry using 2＇, 7＇-dichlorofluorescein diacetate. Endothelial NOS （eNOS）, caveolin-1 protein expressions and caveolin-1/eNOS interaction were analyzed by immunoblotting and immunoprecipitation respectively. Asymmetric dimethylarginine （ADMA） concentration was determined by high-performance liquid chromatography. Results Exposure to 33 mmol/L glucose for 48 hours significantly increased the number of SA-13-gal positive cells. Co-incubation with aspirin markedly inhibited SA-13-gal activity dose-dependently. Aspirin increased NOS activity with eNOS protein expression unchanged and increased NO levels and alleviated oxidative stress. Consistent with these findings, caveolin-1 expression, caveolin-1/eNOS interaction and ADMA accumulation were also decreased. All the inhibitory effects of aspirin on senescence were completely obliterated by L-NAME, the NOS inhibitor. Conclusion The anti-senescent effects of aspirin are fulfilled by increasing NO production via the up-regulation of NOS act展开更多
Objective: To examine the prognostic value of serum levels of asymmetric dimethylarginine(ADMA)in patients with stable coronary heart disease(CHD) thus explore a potential biomarker of "toxin syndrome" in CH...Objective: To examine the prognostic value of serum levels of asymmetric dimethylarginine(ADMA)in patients with stable coronary heart disease(CHD) thus explore a potential biomarker of "toxin syndrome" in CHD.Methods: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event(RCE) during 1-year fol ow-up. Serum levels of ADMA at the start of fol ow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. Results: Based on the crude model, subjects in the 2 highest ADMA quartiles showed signi?cantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio(OR) 4.09, 95%confidence interval(CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model(OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model(OR 6.64,95% CI 1.40 to 31.49; OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein(hs CRP) showed better predictive power with areas under the receiver operator characteristic curves(0.779) than the model of either ADMA(0.694) or hs CRP(0.636). Conclusion:Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is Chi CTR-PRNRC-07000012]展开更多
Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 （PRMT1）/dimethyl...Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 （PRMT1）/dimethylarginine dimethylaminohydrolase （DDAH）/ asymmetrical dimethylarginine （ADMA）/NO synthase （NOS） pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate （EGCG） is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups： one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of O, 10 mg kg-1, and 100 mg kg-1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure （ICP） measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMTI/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase （SOD） and malondialdehyde （MDA） levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure （MAP） was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH 1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.展开更多
AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15...AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.展开更多
Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa prote...Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity.NO increases gastric mucosa blood flow,regulates the secretion of mucus and bicarbonate,and inhibits the secretion of gastric juice.Asymmetric dimethylarginine(ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase.The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity.Besides inhibiting NO synthesis,ADMA also directly induces oxidative stress and cell apoptosis,and participates in inflammation reaction.Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases.ADMA also mediates gastric ulcer injury induced by ethanol,stress,helicobacter pylori and indomethacin.The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood.It is widely accepted that NO bioavailability decrease is the majority reason.Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury.ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder.Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases,it is unknown in gastrointestinal disease.The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats.Thus,ADMA might be a candidate of therapeutic target in gastric mucosa damage.展开更多
Cirrhosis is associated with marked abnormalities in the circulatory function that involve a reduction in systemic vascular resistance. An important cause of this vasodilatation is the increased production or activity...Cirrhosis is associated with marked abnormalities in the circulatory function that involve a reduction in systemic vascular resistance. An important cause of this vasodilatation is the increased production or activity of nitric oxide(NO) in the splanchnic circulation. During portal hypertension and cirrhosis an increased endothelial NO synthase(e NOS) activity is demonstrated in splanchnic vessels. In contrast, the activity of e NOS in the cirrhotic liver is decreased, which suggests a different regulation of e NOS in the liver and in the splanchnic vessels. Asymmetric dimethylarginine(ADMA) is an endogenous NO inhibitor and higher plasma levels of ADMA are related to increased cardiovascular risk in both the general population and among patients with cirrhosis. It has been demonstrated that the liver is a key player in the metabolism of ADMA. This observation was further supported by investigations in human patients, showing a close correlation between ADMA plasma levels and the degree of hepatic dysfunction. ADMA is degraded to citrulline and dimethylamine by dimethylarginine dimethylaminohydrolases(DDAHs). DDAHs are expressed as type 1 and 2 isoforms and are widely distributed in various organs and tissues, including the liver. In this review, we discuss experimental and clinical data that document the effects of dimethylarginines on vascular function in cirrhosis. Our increasing understanding of the routes of synthesis and metabolism of methylarginines is beginning to provide insights into novel mechanisms of liver disease and allowing us to identify potential therapeutic opportunities.展开更多
Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolyt...Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.展开更多
Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separatio...Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.展开更多
Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is ...Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzym展开更多
Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders.Nitric oxide is generated by nitric oxide synthases from the amino acid...Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders.Nitric oxide is generated by nitric oxide synthases from the amino acid L-arginine.L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines,asymmetric dimethylarginine,and symmetric dimethylarginine,by methylation.Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial dysfunction.This review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care treatment.Conditions addressed in this review include intracerebral hemorrhage,aneurysmal subarachnoid hemorrhage,and traumatic brain injury.Recent therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke.展开更多
Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis...Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase(DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this doubleblind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, Sma I restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2(-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models(GG and CG), while 89.13% of healthy control subjects had dominant genetic models(CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls(P = 0.0002). The frequency of G alleles in the leukoaraiosis patients(71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower(χ~2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes(Kruskal展开更多
AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric...AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric dimethylarginine(SDMA),and nitric oxide(NO) plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS:A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase(DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.展开更多
Objective:To study the correlation of serum soluble endoglin (sEng) and asymmetric dimethylarginine (ADMA) levels with placental hypoxia injury and cell apoptosis in patients with preeclampsia.Methods:56 patients diag...Objective:To study the correlation of serum soluble endoglin (sEng) and asymmetric dimethylarginine (ADMA) levels with placental hypoxia injury and cell apoptosis in patients with preeclampsia.Methods:56 patients diagnosed with preeclampsia in our hospital between May 2014 and March 2016 were selected as PE group, healthy subjects giving birth during the same period were selected as control group, serum was collected to determine sEng and ADMA levels, and the placenta tissue was collected to determine the levels of oxidative stress indexes and cell apoptosis molecules.Results: Serum sEng and ADMA levels of PE group were significantly higher than those of control group (P<0.05);SOD, GSH-Px, CAT, SVCT1, SVCT2, Survivin and XIAP levels in placenta tissue of PE group were significantly lower than those of control group (P<0.05) while Beclin1 and LC3-II/LC-I ratio were significantly higher than those of control group (P<0.05);Beclin1 and LC3-II/LC-I ratio in placenta of patients with high sEng and ADMA levels within PE group were significantly higher than those of patients with low sEng and ADMA levels (P<0.05) while SOD, GSH-Px, CAT, SVCT1, SVCT2, Survivin and XIAP levels were significantly lower than those of patients with low sEng and ADMA levels (P<0.05).Conclusions:Serum sEng and ADMA levels in patients with preeclampsia increase significantly and are closely related to the placental hypoxia injury and cell apoptosis.展开更多
文摘Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.
基金the grant from the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20050610050).
文摘Background Hyperhomocysteinemia （HHcy）-mediated dysfunction of endothelial NO system is an important mechanism for atherosclerotic pathogenesis. Dimethylarginine dimethylaminohydrolase （DDAH） is the key enzyme for degrading asymmetric dimethylarginine （ADMA）, which is an endogenous inhibitor of endothelial nitric oxide （NO） synthase （eNOS）. This study was designed to investigate whether the dysfunction of endothelial NO system originates from HHcy-mediated aberrant methylation modification in promotor region of DDAH2 gene. Methods Human umbilical vein endothelial cells （HUVECs） were cultured to the third generation and treated with homocysteine （Hcy） at different concentrations （0, 10, 30, 100, and 300 μmol/L） for 72 hours. The methylation pattern in promoter region CpG island of DDAH2 gene was analyzed by nested methylation-specific PCR （nMSP）. The mRNA expression of eNOS gene and DDAH2 gene was detected by semi-quantitative RT-PCR. The activity of DDAH2 and eNOS in cells, and the concentrations of ADMA and NO in culture medium were assayed respectively. Results Mild increased concentration of Hcy （10 and 30 μmol/L） induced hypomethylation, while high concentration of Hcy （100 and 300 μmol/L） induced hypermethylation in the promoter CpG island of DDAH2 gene. The mRNA expression of DDAH2 increased in mild enhanced concentration of Hcy, and decreased in high concentration of Hcy correspondingly. The inhibition of DDAH2 activity, the increase of ADMA concentration, the reduction of eNOS activity and the decrease of NO production were all consistently relevant to the alteration of Hcy concentration. Conclusion The increased concentration of Hcy induced aberrant methylation pattern in promotor region of DDAH2 gene and the successive alterations in DDAH/ADMA/NOS/NO pathway, which showed highly relevant and dose-effect relationship. The results suggested that the dysfunction of endothelial NO system induced by HHcy could be partially originated from Hcy-mediated aberrant m
基金Supported by The Department of Biotechnology-Ramalingaswami Fellowship 5 years grant from the Government of India
文摘This review describes the recent developments in the pathobiology of endothelial dysfunction(ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. EDcharacterised by an impaired bioactivity of nitric oxide(NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase(e NOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of e NOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases.
文摘Background Endothelial cell senescence is accelerated under high glucose condition, which may contribute to the vascular complications in the diabetics, tt has been proved that aspirin has multiple cytoprotective effects. This study aimed to investigate the effect of aspirin on high glucose-induced endothelial cell senescence and its possible mechanism. Methods Human umbilical venous endothelial cells were cultured in Dulbecco＇s modified Eagle＇s medium （DMEM） with different treatments including the normal glucose （5.5 mmol/L）, high glucose （33 mmol/L） and aspirin （0.01-1.00 mmol/L） with high glucose. And 300 umol/L L-NAME was added to the culture medium when needed. After 48 hours, SA-13-gal staining was used to evaluate the senescence. Total nitric oxide （NO） production and NO synthase （NOS） activity were measured using Griess reaction and molecular probes of 3-amino-4-aminomethyl-2＇, 7＇- difluorescein, diacetate. The level of intracellular reactive oxygen species was monitored by flow cytometry using 2＇, 7＇-dichlorofluorescein diacetate. Endothelial NOS （eNOS）, caveolin-1 protein expressions and caveolin-1/eNOS interaction were analyzed by immunoblotting and immunoprecipitation respectively. Asymmetric dimethylarginine （ADMA） concentration was determined by high-performance liquid chromatography. Results Exposure to 33 mmol/L glucose for 48 hours significantly increased the number of SA-13-gal positive cells. Co-incubation with aspirin markedly inhibited SA-13-gal activity dose-dependently. Aspirin increased NOS activity with eNOS protein expression unchanged and increased NO levels and alleviated oxidative stress. Consistent with these findings, caveolin-1 expression, caveolin-1/eNOS interaction and ADMA accumulation were also decreased. All the inhibitory effects of aspirin on senescence were completely obliterated by L-NAME, the NOS inhibitor. Conclusion The anti-senescent effects of aspirin are fulfilled by increasing NO production via the up-regulation of NOS act
基金Supported by Chinese National Program of Key Basic Research(No.2006CB504803)Beijing Committee of Science and Technology(No.D08050703020801)the 12th Five-Year Plan of China(No.2013BAI02B01)
文摘Objective: To examine the prognostic value of serum levels of asymmetric dimethylarginine(ADMA)in patients with stable coronary heart disease(CHD) thus explore a potential biomarker of "toxin syndrome" in CHD.Methods: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event(RCE) during 1-year fol ow-up. Serum levels of ADMA at the start of fol ow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. Results: Based on the crude model, subjects in the 2 highest ADMA quartiles showed signi?cantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio(OR) 4.09, 95%confidence interval(CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model(OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model(OR 6.64,95% CI 1.40 to 31.49; OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein(hs CRP) showed better predictive power with areas under the receiver operator characteristic curves(0.779) than the model of either ADMA(0.694) or hs CRP(0.636). Conclusion:Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is Chi CTR-PRNRC-07000012]
文摘Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 （PRMT1）/dimethylarginine dimethylaminohydrolase （DDAH）/ asymmetrical dimethylarginine （ADMA）/NO synthase （NOS） pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate （EGCG） is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups： one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of O, 10 mg kg-1, and 100 mg kg-1 for 12 weeks, respectively. Erectile function was assessed by electrical stimulation of the cavernous nerves with intracavernous pressure （ICP） measurement. After euthanasia, penile tissue was investigated using Western blot and ELISA to assess the PRMTI/DDAH/ADMA/NOS metabolism pathway. Superoxide dismutase （SOD） and malondialdehyde （MDA） levels were detected by colorimetry. We also evaluated smooth muscle contents. The ratio of maximal ICP and mean systemic arterial pressure （MAP） was markedly higher in EGCG-treated aged rats than in untreated aged rats. We found that DDAH 1 and DDAH2 were expressed in cavernosal tissue, and they were downregulated in corpora of aged rats. The administration of EGCG upregulated the expression and activity of DDAH. In contrast, EGCG treatment downregulated the expression of PRMT1 and ADMA content. Moreover, EGCG-treated rats showed an improvement in smooth muscle expression, the ratio of smooth muscle cell/collagen fibril, SOD activity, and MDA levels when compared with untreated aged rats.
基金Supported by Consellería de Sanidad of the Generalitat Valenciana,No.AP-052/08
文摘AIM To evaluate the effects of asymmetric dimethylarginine(ADMA) in renal arteries from portal hypertensive and cirrhotic rats.METHODS Rat renal arteries from Sham(n = 15), pre-hepatic portal hypertension(PPVL; n = 15) and bile duct ligation and excision-induced cirrhosis(BDL; n = 15) were precontracted with norepinephrine, and additional contractions were induced with ADMA(10-6-10-3 mol/L), an endogenous inhibitor of nitric oxide(NO) synthase. Concentration-response curves to acetylcholine(1 × 10-9^(-3) × 10^(-6) mol/L) were determined in precontractedrenal artery segments with norepinephrine in the absence and in the presence of ADMA. Kidneys were collected to determine the protein expression and activity of dimethylarginine dimethylaminohydrolase(DDAH), an enzyme that catabolizes ADMA. RESULTS In renal arteries precontracted with norepinephrine, ADMA caused endothelium-dependent contractions. The pD 2 values to ADMA were similar in the Sham and PPVL groups(4.20 ± 0.08 and 4.11 ± 0.09, P > 0.05, respectively), but were lower than those of the BDL group(4.79 ± 0.16, P < 0.05). Acetylcholine-induced endothelium-dependent relaxation that did not differ, in terms of p D2 and maximal relaxation, among the 3 groups studied. Treatment with ADMA(3 × 10^(-4) mol/L) inhibited acetylcholine-induced relaxation in the 3 groups, but the inhibition was higher(P < 0.05) in the BDL group compared with that for the Sham and PPVL groups. The m RNA and protein expression of DDAH-1 were similar in kidneys from the three groups. Conversely, DDAH-2 expression was increased(P < 0.05) in PPVL and further enhanced(P < 0.05) in the BDL group. However, renal DDAH activity was significantly decreased in the BDL group. CONCLUSION Cirrhosis increased the inhibitory effect of ADMA on basal- and induced-release of NO in renal arteries, and decreased DDAH activity in the kidney.
文摘Nitric oxide(NO),a multifunctional endogenous gas molecule,is metabolized from L-arginine by enzymatic reaction in the presence of nitric oxide synthase.NO,an important gas signaling molecule,is a gastric mucosa protective factor that contributes significantly to maintain normal gastric mucosa integrity.NO increases gastric mucosa blood flow,regulates the secretion of mucus and bicarbonate,and inhibits the secretion of gastric juice.Asymmetric dimethylarginine(ADMA) has been identified as the major endogenous inhibitor of nitric oxide synthase.The function of ADMA is to decrease NO production via inhibiting nitric oxide synthase activity.Besides inhibiting NO synthesis,ADMA also directly induces oxidative stress and cell apoptosis,and participates in inflammation reaction.Its systemic accumulation was observed in conjunction with several cardiovascular and metabolic diseases.ADMA also mediates gastric ulcer injury induced by ethanol,stress,helicobacter pylori and indomethacin.The mechanism of ADMA directly producing adverse effect in gastric mucosa is incompletely understood.It is widely accepted that NO bioavailability decrease is the majority reason.Promotion of apoptosis and aggravation of inflammation may be other important mechanisms of ADMA-induced gastric injury.ADMA might be a novel clinical and experimental biomarker related to gastric mucosa disorder.Although therapeutic tool targeting to ADMA is available in multiple cardiovascular diseases,it is unknown in gastrointestinal disease.The strategy to inhibit ADMA is beneficial to gastric ulcer induced by ethanol in rats.Thus,ADMA might be a candidate of therapeutic target in gastric mucosa damage.
基金Supported by University of Valencia,Instituto de Salud Carlos III,and Consellería de Sanidad,Generalitat Valenciana
文摘Cirrhosis is associated with marked abnormalities in the circulatory function that involve a reduction in systemic vascular resistance. An important cause of this vasodilatation is the increased production or activity of nitric oxide(NO) in the splanchnic circulation. During portal hypertension and cirrhosis an increased endothelial NO synthase(e NOS) activity is demonstrated in splanchnic vessels. In contrast, the activity of e NOS in the cirrhotic liver is decreased, which suggests a different regulation of e NOS in the liver and in the splanchnic vessels. Asymmetric dimethylarginine(ADMA) is an endogenous NO inhibitor and higher plasma levels of ADMA are related to increased cardiovascular risk in both the general population and among patients with cirrhosis. It has been demonstrated that the liver is a key player in the metabolism of ADMA. This observation was further supported by investigations in human patients, showing a close correlation between ADMA plasma levels and the degree of hepatic dysfunction. ADMA is degraded to citrulline and dimethylamine by dimethylarginine dimethylaminohydrolases(DDAHs). DDAHs are expressed as type 1 and 2 isoforms and are widely distributed in various organs and tissues, including the liver. In this review, we discuss experimental and clinical data that document the effects of dimethylarginines on vascular function in cirrhosis. Our increasing understanding of the routes of synthesis and metabolism of methylarginines is beginning to provide insights into novel mechanisms of liver disease and allowing us to identify potential therapeutic opportunities.
文摘Asymmetric-dimethylarginine(ADMA) competes with L-arginine for each of the three isoforms of nitric oxide synthase:endothelial;neuronal;inducible.ADMA is synthesized by protein methyltransferases followed by proteolytic degradation.ADMA is metabolized to citrulline and dimethylamine,by dimethylarginine dimethylaminohydrolase(DDAH) and enters cells through cationic amino-acid transporters extensively expressed in the liver.The liver plays a crucial role in ADMA metabolism by DDAH-1 and,as has been recently demonstrated,it is also responsible for ADMA biliary excretion.A correlation has been demonstrated between plasma ADMA levels and the degree of hepatic dysfunction in patients suffering from liver diseases with varying aetiologies:plasma ADMA levels are increased in patients with liver cirrhosis,alcoholic hepatitis and acute liver failure.The mechanism by which liver dysfunction results in raised ADMA concentrations is probably due to impaired activity of DDAH due to severe inflammation,oxidative stress,and direct damage to DDAH.High plasma ADMA levels are also relevant as they are associated with the onset of multiorgan failure(MOF).Increased plasma concentration of ADMA was identified as an independent risk factor for MOF in critically-ill patients causing enhanced Intensive Care Unit mortality:a significant reduction in nitric oxide synthesis,leading to malperfusion in various organs,eventually culminating in multi organs dysfunction.
文摘Herein, we present a novel method of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) determination within biological samples using protein precipitation and LC/MS/MS. Chromatographic separation of ADMA and SDMA was successfully performed using a silica column with optimized elution, or mobile phase, of 10 mM ammonium acetate buffer H2O/methanol/acetonitrile (20/30/45, v/v) at pH 4. The calibration ranges were 0.50 – 50.0 μg●mL-1, and good linearities were obtained for all compounds ( γ > 0.99). The intra- and inter-assay accuracies with recoveries and precisions at three concentration levels (i.e. 1.00, 5.00 and 25.0 μg●mL-1) were better than 86.9% and 7.36%, respectively. The analytical performance of the method was evaluated by determination of compounds in plasma, urine and tissues from male BALBc/J mice. For the first time, we were able to characterize the distribution of ADMA, SDMA and ADMA/SDMA in plasma, urine, brain, heart, kidneys, liver, lungs, pancreas and spleen. Additionally, we demonstrated that the ADMA/SDMA ratio in the brain was approximately 10-fold lower than all the other biological samples. Only 10 μL of plasma, 1 μL of urine and about 25 mg of tissues were required. These results suggest that the developed methodology was useful in ADMA and SDMA determination within biological samples.
文摘Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzym
文摘Nitric oxide is an important mediator of vascular autoregulation and is involved in pathophysiological changes after acute neurological disorders.Nitric oxide is generated by nitric oxide synthases from the amino acid L-arginine.L-arginine can also serve as a substrate for arginases or lead to the generation of dimethylarginines,asymmetric dimethylarginine,and symmetric dimethylarginine,by methylation.Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and can lead to endothelial dysfunction.This review discusses the role of L-arginine metabolism in patients suffering from acute and critical neurological disorders often requiring neuro-intensive care treatment.Conditions addressed in this review include intracerebral hemorrhage,aneurysmal subarachnoid hemorrhage,and traumatic brain injury.Recent therapeutic advances in the field are described including current randomized controlled trials for traumatic brain injuries and hemorrhagic stroke.
基金supported by the Foundation of Harbin Science Technology Bureau of China,No. 2014RFQGJ042 (to YF)Harbin Medical University Scientific Research Innovation Fund of China,No. 2016LCZX06 (to QG)the Natural Science Foundation of Heilongjiang of China,No. H2016027 (to QG)。
文摘Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase(DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this doubleblind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, Sma I restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2(-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models(GG and CG), while 89.13% of healthy control subjects had dominant genetic models(CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls(P = 0.0002). The frequency of G alleles in the leukoaraiosis patients(71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower(χ~2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes(Kruskal
文摘AIM:To analyze the change of dimethylarginine plasma levels in cirrhotic patients receiving transjugular intrahepatic portosystemic shunt(TIPS).METHODS:To determine arginine,asymmetric dimethylarginine(ADMA),symmetric dimethylarginine(SDMA),and nitric oxide(NO) plasma levels,blood samples were collected from the superior cava,hepatic,and portal vein just before,directly after,and 3 mo after TIPS-placement.RESULTS:A significant increase in the arginine/ADMA ratio after TIPS placement was shown.Moreover,TIPS placement enhanced renal function and thereby decreased systemic SDMA levels.In patients with renal dysfunction before TIPS placement,both the arginine/ADMA ratio and creatinine clearance rate increased significantly,while this was not the case in patients with normal renal function before TIPS placement.Hepatic function did not change significantly after TIPS placement and no significant decline in ADMA plasma levels was measured.CONCLUSION:The increase of the arginine/ADMA ratio after TIPS placement suggests an increase in intracellular NO bioavailability.In addition,this study suggests that TIPS placement does not alter dimethylarginine dimethylaminohydrolase(DDAH) activity and confirms the major role of the liver as an ADMA clearing organ.
文摘Objective:To study the correlation of serum soluble endoglin (sEng) and asymmetric dimethylarginine (ADMA) levels with placental hypoxia injury and cell apoptosis in patients with preeclampsia.Methods:56 patients diagnosed with preeclampsia in our hospital between May 2014 and March 2016 were selected as PE group, healthy subjects giving birth during the same period were selected as control group, serum was collected to determine sEng and ADMA levels, and the placenta tissue was collected to determine the levels of oxidative stress indexes and cell apoptosis molecules.Results: Serum sEng and ADMA levels of PE group were significantly higher than those of control group (P<0.05);SOD, GSH-Px, CAT, SVCT1, SVCT2, Survivin and XIAP levels in placenta tissue of PE group were significantly lower than those of control group (P<0.05) while Beclin1 and LC3-II/LC-I ratio were significantly higher than those of control group (P<0.05);Beclin1 and LC3-II/LC-I ratio in placenta of patients with high sEng and ADMA levels within PE group were significantly higher than those of patients with low sEng and ADMA levels (P<0.05) while SOD, GSH-Px, CAT, SVCT1, SVCT2, Survivin and XIAP levels were significantly lower than those of patients with low sEng and ADMA levels (P<0.05).Conclusions:Serum sEng and ADMA levels in patients with preeclampsia increase significantly and are closely related to the placental hypoxia injury and cell apoptosis.
