Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 k...Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 kDa gelatinase A/type IV collagenase (MMP-2), and 92 kDa gelatinase B/type IV collagenase (MMP-9) dissolve extracellular matrix (ECM) and may initiate and Promote angiogenesis. TIMP-1, TIMP-2, TIMP-3, and possibly,TIMP-4 inhibit neovascularisation. A new paradigm is emerging that matrilysin (MMP-7), MMP-9, and metalloelastase (MMP-12) may block angiogehesis by converting plasndnogen to angiostatin, which is one of the most potent angiogenesis antagonists. MMPs and TIMPs play a complex role in regulating angiogenesis. An understanding of the biochemical and cellular pathways and mechanisms of angiogenesis will provide importal information to allow the control of angiogenesis, e.g. the stimulation of angiogenesis for coronary collateral circulation formation; while the inhibition for treating arthritis and cancer.展开更多
Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of ...Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.展开更多
Background Excessive deposition of extraceUular matrix （ECM） in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative path...Background Excessive deposition of extraceUular matrix （ECM） in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was understaken to investigate the activity of matrix metalloproteinase-2 （MMP-2）, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 （TIMP-2） in kidney tissues of diabetic rats, and to explore the degradative pathway of type Ⅳ collagen （Ⅳ-C） and the renal protective effects of ACE inhibition- benazepril.展开更多
The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS ...The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.展开更多
AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 ...AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.展开更多
Background Transforming growth factor （TGF） β1-Smads signal plays an important role in cardiac remodeling following myocardial infarction （MI）. In addition, both angiotensin converting enzyme inhibitor （ACEI） a...Background Transforming growth factor （TGF） β1-Smads signal plays an important role in cardiac remodeling following myocardial infarction （MI）. In addition, both angiotensin converting enzyme inhibitor （ACEI） and angiotensin Ⅱ type Ⅰ receptor blocker （ARB） can effectively prevent left ventricular remodeling. The current study focused on whether the combination of ACEI and ARB is more beneficial for preventing ventricular remodeling and whether Smad proteins mediate this beneficial effect. Methods MI was induced by ligating the left anterior descending coronary artery in rats. Twenty-four hours after ligation, the survived rats were randomly divided into five groups and treated for 8 weeks： placebo group, ACEI group （benazepril 10 mg · kg^-1· d^-1）, ARB group （irbesartan 50mg · kg^-1· d^-1）, ACEI＋ARB group （benazepril 10 mg · kg^-1· d^-1＋irbesartan 50 mg · kg^-1· d^-1） and control group （sham-operated rats）. After 8 weeks, we examined the following indexes： the ratio of ventricular weight to body weight （VW/BW）, left ventricular end diastolic dimension （LVDd）, ejection fraction （EF）, fractional shortening （FS）, ratio of E-wave to A-wave velocity, collagen of noninfarcted zone, the mRNA expression of TGFβ1, Smad 2, and Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot. Results VW/BW significantly increased in the placebo groups compared with that in the control group （P〈0.01）. This increase was limited in ACEI, ARB, and combined groups （P〈0.01 compared with placebo group）. There was no significant difference among the three actively treated groups. Collagen was increased in placebo group （5.68±0.5）% compared with that in control group （P〈0.01）. ACEI, ARB and combined treatment attenuated this increase of collagen [（4.3 ± 0.5）%, （3.5 ± 0.5）%, （3.2± 0.4）%] in comparison with that in placebo group （P〈0.01 respectively）. Combined treatmen展开更多
AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： P...AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.展开更多
Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive...Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P <0.05). Carotid internal diameter,distensibility and stiffness were similar among the DD,ID and II genotypes of ACE ( P >0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%,and 79.5% vs 40.5%,respectively, P <0.001). In multiple stepwise regression analysis,independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes ( P <0.001),age ( P <0.001) and carotid internal diameter ( P =0.032). Moreover,triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype ( P <0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT,but not to internal diameter,distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.展开更多
Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical...Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.展开更多
文摘Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 kDa gelatinase A/type IV collagenase (MMP-2), and 92 kDa gelatinase B/type IV collagenase (MMP-9) dissolve extracellular matrix (ECM) and may initiate and Promote angiogenesis. TIMP-1, TIMP-2, TIMP-3, and possibly,TIMP-4 inhibit neovascularisation. A new paradigm is emerging that matrilysin (MMP-7), MMP-9, and metalloelastase (MMP-12) may block angiogehesis by converting plasndnogen to angiostatin, which is one of the most potent angiogenesis antagonists. MMPs and TIMPs play a complex role in regulating angiogenesis. An understanding of the biochemical and cellular pathways and mechanisms of angiogenesis will provide importal information to allow the control of angiogenesis, e.g. the stimulation of angiogenesis for coronary collateral circulation formation; while the inhibition for treating arthritis and cancer.
文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.
基金This study was supported by a grant from the Natural Science Foundation of Shandong Province (No. Y2002C35).
文摘Background Excessive deposition of extraceUular matrix （ECM） in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was understaken to investigate the activity of matrix metalloproteinase-2 （MMP-2）, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 （TIMP-2） in kidney tissues of diabetic rats, and to explore the degradative pathway of type Ⅳ collagen （Ⅳ-C） and the renal protective effects of ACE inhibition- benazepril.
基金supported by Training Program of the National Major Research Plan(91339108)General Program(81370362,81170246)of the National Natural Science Foundation of Chinathe National Basic Research Program of China(2014CB542300)
文摘The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.
文摘AIM To study the role of interleukin 1β converting enzyme (ICE) in antitumor drug induced apoptosis in tumor cells. METHODS Morphological changes in human esophageal carcinoma Eca 109 cells after treated with 5 fluorouracil (5 FU) were observed under light and electron microscope. Expression of ICE in the tumor cells exposed to 5 FU was examined by the immunocytochemical method. RESULTS The cells treated with 5 FU displayed disappearance of nucleoli, chromatin gathering under nuclear envelope, karyorrhexis, budding and the formation of apoptotic bodies. The expression of ICE was negative in control cells, and 5 FU could induce the ICE expression in Eca 109 cells undergoing apoptosis. The number and the staining intensity of positive cells increased with the extension of action time. CONCLUSION 5 FU may induce apoptosis in human esophageal carcinoma Eca 109 cells; ICE gene may be involved in the regulation of 5 FU induced apoptosis; and ICE protein may mediate apoptosis induced by 5 FU.
基金The project was supported by a grant from the Natural Science Foundation of Heilongjiang Province (No. D0239) and the Post Doctor Foundation of Heilongjiang Province.
文摘Background Transforming growth factor （TGF） β1-Smads signal plays an important role in cardiac remodeling following myocardial infarction （MI）. In addition, both angiotensin converting enzyme inhibitor （ACEI） and angiotensin Ⅱ type Ⅰ receptor blocker （ARB） can effectively prevent left ventricular remodeling. The current study focused on whether the combination of ACEI and ARB is more beneficial for preventing ventricular remodeling and whether Smad proteins mediate this beneficial effect. Methods MI was induced by ligating the left anterior descending coronary artery in rats. Twenty-four hours after ligation, the survived rats were randomly divided into five groups and treated for 8 weeks： placebo group, ACEI group （benazepril 10 mg · kg^-1· d^-1）, ARB group （irbesartan 50mg · kg^-1· d^-1）, ACEI＋ARB group （benazepril 10 mg · kg^-1· d^-1＋irbesartan 50 mg · kg^-1· d^-1） and control group （sham-operated rats）. After 8 weeks, we examined the following indexes： the ratio of ventricular weight to body weight （VW/BW）, left ventricular end diastolic dimension （LVDd）, ejection fraction （EF）, fractional shortening （FS）, ratio of E-wave to A-wave velocity, collagen of noninfarcted zone, the mRNA expression of TGFβ1, Smad 2, and Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot. Results VW/BW significantly increased in the placebo groups compared with that in the control group （P〈0.01）. This increase was limited in ACEI, ARB, and combined groups （P〈0.01 compared with placebo group）. There was no significant difference among the three actively treated groups. Collagen was increased in placebo group （5.68±0.5）% compared with that in control group （P〈0.01）. ACEI, ARB and combined treatment attenuated this increase of collagen [（4.3 ± 0.5）%, （3.5 ± 0.5）%, （3.2± 0.4）%] in comparison with that in placebo group （P〈0.01 respectively）. Combined treatmen
基金Supported by Fundacode Amparo à Pesquisa do Estado de Minas Gerais, Conselho Nacional de Desenvolvimento Científico e Tecnológico, FAPEMIG/CNPQ-PRONEX (Grupos de Excelência),Ministério de Ciência e Tecnologia/CNPq/ FAPEMIG-INCT-Nano-Biofar
文摘AIM： To measure circulating angiotensins at different stages of human cirrhosis and to further evaluate a possible relationship between renin angiotensin system （RAS） components and hemodynamic changes. METHODS： Patients were allocated into 4 groups： mild-to-moderate liver disease （MLD）, advanced liver disease （ALD）, patients undergoing liver transplantation, and healthy controls. Blood was collected to determine plasma renin activity （PRA）, angiotensin （Ang） Ⅰ, Ang Ⅱ, and Ang-（1-7） levels using radioimmunoassays. During liver transplantation, hemodynamic parameters were determined and blood was simultaneously obtained from the portal vein and radial artery in order to measure RAS components. RESULTS： PRA and angiotensins were elevated in ALD when compared to MLD and controls （P 〈 0.05）. In contrast, Ang Ⅱ was significantly reduced in MLD. Ang-（1-7）/Ang Ⅱ ratios were increased in MLD when compared to controls and ALD. During transplantation, Ang Ⅱ levels were lower and Ang-（1-7）/Ang Ⅱ ratios were higher in the splanchnic circulation than in the peripheral circulation （0.52 ± 0.08 vs 0.38 ±0.04, P 〈 0.02）, whereas the peripheral circulating Ang Ⅱ/Ang Ⅰ ratio was elevated in comparison to splanchnic levels （0.18 ±0.02 vs 0.13 ±0.02, P 〈 0.04）. Ang-（1-7）/ Ang Ⅱ ratios positively correlated with cardiac output （r = 0.66） and negatively correlated with systemic vascular resistance （r = -0.70）. CONCLUSION： Our findings suggest that the relationship between Ang-（1-7） and Ang Ⅱ may play a role in the hemodynamic changes of human cirrhosis.
文摘Background This study was designed to investigate the relationships between changes in the structure and function of carotid arteries and angiotensin converting enzyme (ACE) gene polymorphism in Chinese hypertensive subjects. Methods Multiplex polymerase chain reaction amplification was used to evaluate the ACE gene insertion/deletion (I/D) polymorphism. High-resolution B-mode ultrasound examinations were performed to detect parameters of carotid artery remodeling. Results Intima-media thickness (IMT) was significantly different among the DD, ID and II genotypes of ACE (DD>ID>II, P <0.05). Carotid internal diameter,distensibility and stiffness were similar among the DD,ID and II genotypes of ACE ( P >0.05) in hypertensive subjects. The frequency of the DD gene and D allele of ACE were higher in patients with thickening carotid than in patients with normal carotid (70.4% vs 24.1%,and 79.5% vs 40.5%,respectively, P <0.001). In multiple stepwise regression analysis,independent risk factors for increased carotid IMT in hypertensive subjects were ACE genotypes ( P <0.001),age ( P <0.001) and carotid internal diameter ( P =0.032). Moreover,triglycerides and total cholesterol were higher in patients with the DD genotype than in those with the II genotype ( P <0.05). Conclusions The I/D polymorphism of the ACE gene was related to IMT,but not to internal diameter,distensibility and stiffness of the carotid in Chinese hypertensive subjects. ACE gene polymorphism was a main risk factor for increased carotid IMT. These results may imply that there is a link between lipid metabolism and ACE genotype polymorphism in Chinese hypertensive subjects.
基金supported by the Beijing Natural Science Foundation Program(Grant number:5102040)the Open Foundation of the Beijing Key Laboratory of Hypertension Research(Grant number:2015GXYB01)
文摘Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperhomocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serum Hcy levels and decreased after folate treatment.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was decreased in the Wistar folate group.Angiotensin II receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serum H2S and kidney cystathionineγ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treatment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might mediate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
