The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nico...The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nicotinamide adenine dinucleotide phosphate （NADPH） oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac 1 was dependent on the levels of intracellular H202. Puerarin blocked the phosphorylation of extracellular regulated protein kinases （ERK）1/2, abolished activator protein （AP）-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H202-dependent Racl activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregu- lation of catalase expression and H202-dependent Racl activation.展开更多
Background It＇s established that Angiotensin Ⅱ and its receptors are involved in intimal hyperplasia after balloon injury and stent restenosis. Recent evidence also suggests that statins have some anti-intimal hyper...Background It＇s established that Angiotensin Ⅱ and its receptors are involved in intimal hyperplasia after balloon injury and stent restenosis. Recent evidence also suggests that statins have some anti-intimal hyperplasia effects. In this study, the effect of Rosuvastatin on expression of angiotensin Ⅱ receptors in rat aortic endothelium after balloon injury is therefore investigated. Methods All 52 Wistar Kyoto rats were established to aorta injury models by 2F balloon catheter, then were randomly divided into sham operation group, aorta injury group and Rosuvastatin-treatment group. After 14 days, the aortic specimens of the animals were harvested and performed immunohistochemistry and determination of molecular biology. Results The results showed that （i） The 14 days-balloon injury induced obvious intima thickening （P 〈 0.01）, however, the phenomenon was reduced by 14 daystreatment with Rosuvastatin （P 〈 0.01）. （ii） The expressions of angiotention Ⅱ type Ⅰ （AT1） and type Ⅱ （AT2） receptor mRNA and protein were markedly up-regulated by the balloon injury （P 〈 0.01）, after 14 days-treatment with Rosuvastatin, the expression of AT1 receptor mRNA and its protein was decreased （P 〈 0.01）, but the expression of AT2 receptor mRNA and its protein was further increased （P 〈 0.05）. Conclusion In this study, we observed that the balloon injury induced-intima thickening was reduced by Rosuvastatin in rats, which might be linked with the regulation of expression of angiotensin Ⅱ receptors.展开更多
基金supported by the National S&T Major Special Project on Major New Drug Innovation(No.2012ZX09301002-001-015)the National Natural Science Foundation of China(No.30772284)
文摘The aims of the present study were to evaluate the effects of puerarin on angiotensin II-induced cardiac fibroblast proliferation and to explore the molecular mechanisms of action. Considering the role of H202 in nicotinamide adenine dinucleotide phosphate （NADPH） oxidase activation, we hypothesized that modulating catalase activity would be a potential target in regulating the redox-sensitive pathways. Our results showed that the activation of Rac 1 was dependent on the levels of intracellular H202. Puerarin blocked the phosphorylation of extracellular regulated protein kinases （ERK）1/2, abolished activator protein （AP）-1 binding activity, and eventually attenuated cardiac fibroblast proliferation through the inhibition of H202-dependent Racl activation. Further studies revealed that angiotensin II treatment resulted in decreased catalase protein expression and enzyme activity, which was disrupted by puerarin via the upregulation of catalase protein expression at the transcriptional level and the prolonged protein degradation. These findings indicated that the anti-proliferation mechanism of puerarin was mainly through blocking angiontensin II-triggered downregu- lation of catalase expression and H202-dependent Racl activation.
基金supported by Science and Technology Bureau of Qingdao City (Grant No. 02-2-kj-yn-25)
文摘Background It＇s established that Angiotensin Ⅱ and its receptors are involved in intimal hyperplasia after balloon injury and stent restenosis. Recent evidence also suggests that statins have some anti-intimal hyperplasia effects. In this study, the effect of Rosuvastatin on expression of angiotensin Ⅱ receptors in rat aortic endothelium after balloon injury is therefore investigated. Methods All 52 Wistar Kyoto rats were established to aorta injury models by 2F balloon catheter, then were randomly divided into sham operation group, aorta injury group and Rosuvastatin-treatment group. After 14 days, the aortic specimens of the animals were harvested and performed immunohistochemistry and determination of molecular biology. Results The results showed that （i） The 14 days-balloon injury induced obvious intima thickening （P 〈 0.01）, however, the phenomenon was reduced by 14 daystreatment with Rosuvastatin （P 〈 0.01）. （ii） The expressions of angiotention Ⅱ type Ⅰ （AT1） and type Ⅱ （AT2） receptor mRNA and protein were markedly up-regulated by the balloon injury （P 〈 0.01）, after 14 days-treatment with Rosuvastatin, the expression of AT1 receptor mRNA and its protein was decreased （P 〈 0.01）, but the expression of AT2 receptor mRNA and its protein was further increased （P 〈 0.05）. Conclusion In this study, we observed that the balloon injury induced-intima thickening was reduced by Rosuvastatin in rats, which might be linked with the regulation of expression of angiotensin Ⅱ receptors.
