Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predic...Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.展开更多
AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND...AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.展开更多
Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed t...Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.展开更多
AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ（AT1）receptor antagonist inpreventing hepatic fibrosis caused by CCl<sub>4</sub>administration in rats;to investigate whether ornot there are ex...AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ（AT1）receptor antagonist inpreventing hepatic fibrosis caused by CCl<sub>4</sub>administration in rats;to investigate whether ornot there are expression of AT 1 receptors onhepatic stellate cells;and to observe the effectof Ang Ⅱ on proliferation and ECM synthesis ofcultured HSCs.METHODS Studies were conducted in maleSprague-Dawley rats.Except for thehepatofibrotic model group and the controlgroup,in three treated groups,either enalapril（5 mg/kg）,or Iosartan（10 mg/kg）,or enalapril+Iosartan were given to the fibrotic rats bydaily gavage,and saline vehicle was given tomodel and normal control rats.After 6 weeks,liver fibrosis was assessed directly by hepaticmorphometric analysis,which has beenconsidered the gold standard for thequantification of fibrosis.The expressions of AT1 receptors and（α-mooth muscle actin,α-SMA）in liver tissue or isolated hepatic stellate cells（HSCs）were detected by immunohistochemicaltechniques.The effect of Ang Ⅱ on HSCproliferation was determined by MTT method.Effect of Ang Ⅱ on collagen synthesis of HSCswas determined by <sup>3</sup>H-proline incorporation.RESULTS Contrasted to the fibrosis in rats ofthe model group,groups of rats treated with either enalapril or Iosartan,or a combination oftwo drugs showed a limited expansion of theinterstitium（4.23±3.70 vs 11.22±4.79,P【0.05）,but no difference was observedamong three treated groups（5.38±3.43,4.96±2.96,4.23±2.70,P】0.05）.Expression of AT 1receptors was found in fibrotic interstitium offibrotic rats,whereas in normal control rats theywere limited to vasculature only to a very slightdegree.AT 1 receptors were also expressed onactivated HSCs in the culture.At concentrationsfrom 10<sup>-9</sup>to 10<sup>-5</sup>mol/L,Ang Ⅱ stimulated HSCproliferation in culture in a dose-dependentmanner.Increasing Ang Ⅱ concentrationsproduced corresponding increases in <sup>3</sup>H-prolineincorporation.Differences among groups were significant.CONCL展开更多
Objective To review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.Data sources A comprehensive search of the PubMed literatures without restriction on the publi...Objective To review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.Study selection Articles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.Results The ligands as well as construction and tissue distribution of vitamin D receptor were summarized.Pathogenesis of diabetic nephropathy was analyzed.The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system,anti-inflammation,anti-fibrosis and the reduction of proteinuria were reviewed.Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.Conclusion Our study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.展开更多
文摘Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.
文摘AIM To investigate effect of losartan,an AT1receptor antagonist,on hepatic fibrosis induced byCCl<sub>;</sub>and to determine whether or not AT1receptors are expressed on hepatic stellate cells,METHODS AND RESULTS Fifty male Sprague-Dawley rats,weighing（180±20）g,wererandomized into five groups（control group,modelgroup,and three losartan treated groups）,inwhich all rats were given the subcutaneousinjection of 40% CCl<sub>4</sub>（every 3 days for 6 weeks）except for rats of control group.Rats of losartan-treated groups were treated with losartan（20 mg/kg,10 mg/kg,5 mg/kg,daily gavage）,After 6weeks liver tissue and serum samples of all ratswere examined.Serum hyaluronic acid（HA）,procollagen typeⅢ（PCⅢ）were detected byradioimmunoassays,van Giesion collagen stainingwas used to evaluate the extracellular matrix of ratswith liver fibrosis.The expression of AT1receptors,transforming growth factor-beta（TGF-β）,and alpha-smooth muscle actin（a-SMA）inliver tissue were determined byimmunohistochemical techniques.Compared withmodel group,serum ALT and AST of losartan-treated groups were significantly reduced（t=4.20,P【0.01 and t=4.57,P【0.01）.Serum HAand PCⅢalso had significant differences（t=3.53,P【0.01 and t=2.20,P【0.05）.Thedegree of fibrosis was improved by losartan and correlated with the expressions of AT1 receptors,TGF-β,and α-SMA in liver tissue.CONCLUSION AT1 receptor antagonist,losartan,could limit the progression of the hepatic fibrosisinduced by CCl<sub>4</sub>.The mechanism may be related tothe decrease in the expression of AT1 receptorsand TGF-β,ameliorating the injury of hepatocytes;activation of local renin-angiotensin system mightrelate to hepatic fibrosis;and during progressionof fibrosis,activated hepatic stellate cells mightexpress AT1 receptors.
文摘Background Obstructive sleep apnea （OSA） is the most common cause of resistant hypertension, which has been proposed to result from activation of the renin-angiotensin-aldosterone system （RAAS）. We meta-analyzed the effects of OSA on plasma levels of RAAS components. Methods Full-text studies published on MEDL1NE and EMBASE analyzing fasting plasma levels of at least one RAAS component in adults with OSA with or without hypertension. OSA was diagnosed as an apnea-hypopnea index or respiratory disturbance index 〉 5. Study quality was evaluated using the Newcastle-Ottawa Scale, and heterogeneity was assessed using the 12 statistic. Results from individual studies were synthesized using inverse variance and pooled using a random-effects model. Subgroup analysis, sensitivity analysis, and meta-regression were performed, and risk of publication bias was assessed. Results The meta-analysis included 13 studies, of which 10 reported results on renin （n = 470 cases and controls）, 7 on angiotensin II （AnglI, n = 384）, and 9 on aldosterone （n = 439）. AnglI levels were significantly higher in OSA than in controls [mean differences = 3.39 ng/L, 95% CI： 2.00-4.79, P 〈 0.00001], while aldosterone levels were significantly higher in OSA with hypertension than OSA but not with hypertension （mean differences = 1.32 ng/dL, 95% CI： 0.58-2.07, P = 0.0005）. Meta-analysis of all studies suggested no significant differences in aldosterone between OSA and controls, but a significant pooled mean difference of 1.35 ng/mL （95% CI： 0.88-1.82, P 〈 0.00001） emerged after excluding one small-sample study. No significant risk of publication bias was detected among all included studies. Conelusions OSA is associated with higher AnglI and aldosterone levels, espe- cially in hypertensive patients. OSA may cause hypertension, at least in part, by stimulating RAAS activity.
文摘AIM To assess the effect of ACE inhibitor andAng Ⅱ type Ⅰ（AT1）receptor antagonist inpreventing hepatic fibrosis caused by CCl<sub>4</sub>administration in rats;to investigate whether ornot there are expression of AT 1 receptors onhepatic stellate cells;and to observe the effectof Ang Ⅱ on proliferation and ECM synthesis ofcultured HSCs.METHODS Studies were conducted in maleSprague-Dawley rats.Except for thehepatofibrotic model group and the controlgroup,in three treated groups,either enalapril（5 mg/kg）,or Iosartan（10 mg/kg）,or enalapril+Iosartan were given to the fibrotic rats bydaily gavage,and saline vehicle was given tomodel and normal control rats.After 6 weeks,liver fibrosis was assessed directly by hepaticmorphometric analysis,which has beenconsidered the gold standard for thequantification of fibrosis.The expressions of AT1 receptors and（α-mooth muscle actin,α-SMA）in liver tissue or isolated hepatic stellate cells（HSCs）were detected by immunohistochemicaltechniques.The effect of Ang Ⅱ on HSCproliferation was determined by MTT method.Effect of Ang Ⅱ on collagen synthesis of HSCswas determined by <sup>3</sup>H-proline incorporation.RESULTS Contrasted to the fibrosis in rats ofthe model group,groups of rats treated with either enalapril or Iosartan,or a combination oftwo drugs showed a limited expansion of theinterstitium（4.23±3.70 vs 11.22±4.79,P【0.05）,but no difference was observedamong three treated groups（5.38±3.43,4.96±2.96,4.23±2.70,P】0.05）.Expression of AT 1receptors was found in fibrotic interstitium offibrotic rats,whereas in normal control rats theywere limited to vasculature only to a very slightdegree.AT 1 receptors were also expressed onactivated HSCs in the culture.At concentrationsfrom 10<sup>-9</sup>to 10<sup>-5</sup>mol/L,Ang Ⅱ stimulated HSCproliferation in culture in a dose-dependentmanner.Increasing Ang Ⅱ concentrationsproduced corresponding increases in <sup>3</sup>H-prolineincorporation.Differences among groups were significant.CONCL
文摘Objective To review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.Data sources A comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.Study selection Articles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.Results The ligands as well as construction and tissue distribution of vitamin D receptor were summarized.Pathogenesis of diabetic nephropathy was analyzed.The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system,anti-inflammation,anti-fibrosis and the reduction of proteinuria were reviewed.Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.Conclusion Our study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.
