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首页> 外文期刊>Cardiovascular therapeutics >Simvastatin Inhibits Glucose-Stimulated Vascular Smooth Muscle Cell Migration Involving Increased Expression of RhoB and a Block of Ras/Akt Signal
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Simvastatin Inhibits Glucose-Stimulated Vascular Smooth Muscle Cell Migration Involving Increased Expression of RhoB and a Block of Ras/Akt Signal

机译：辛伐他汀抑制葡萄糖刺激的血管平滑肌细胞迁移，涉及RhoB的表达增加和Ras / Akt信号的阻滞。

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Background: Diabetic patients are at high risk to develop atherosclerotic cardiovascular disease and have a higher restenotic rate after percutaneous coronary intervention (PCI). Statins improve cardiovascular outcome and reduce restenosis after PCI by inhibiting proliferation and migration of vascular smooth muscle cells (VSMCs). But the effect of statins on diabetes without dyslipidemia was still not fully understood. Our previous study has demonstrated that simvastatin inhibits VSMC proliferation in high glucose status without dyslipidemia, inducing a G0/G1 phase cell cycle growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and upregulation of p53, p21, p16, and p27. Method: Following our previous study, we investigated the mechanism of simvastatin inhibition of VSMC migration in a diabetes-like model (A7r5 cells under high glucose conditions without dyslipidemia). Results: Under high glucose conditions, simvastatin dose-dependently inhibited VSMC migration, decreased PI3K/Akt pathway activity, reduced c-Raf and Ras expression, increased RhoB but not RhoA, Rac1, and Cdc2 expression, dose-dependently inhibited MMP-2, but not MMP-9, activity, and dose-dependently inhibited NF-κB activity. Conclusion: The inhibition of VSMC migration under high glucose conditions was via two different pathways. The first pathway is mevalonate-related but not RhoA protein-related and involves suppression of Ras and PI3K/Akt signals. The second pathway is not mevalonate-related and involves increasing RhoB expression directly.
机译：背景：糖尿病患者发生动脉粥样硬化性心血管疾病的风险较高，经皮冠状动脉介入治疗（PCI）后再狭窄率更高。他汀类药物通过抑制血管平滑肌细胞（VSMC）的增殖和迁移，改善了PCI后的心血管预后并减少了再狭窄。但他汀类药物对没有血脂异常的糖尿病的作用仍未完全了解。我们先前的研究表明，辛伐他汀可在高血糖状态下抑制VSMC增殖，而无血脂异常，可通过作用于pRb上游的多个步骤来诱导G0 / G1期细胞周期生长停滞，包括抑制CDK2 / 4表达和上调p53，p21， p16和p27。方法：在我们先前的研究之后，我们研究了辛伐他汀抑制糖尿病样模型（高血糖条件下的A7r5细胞，无血脂异常）中VSMC迁移的机制。结果：在高葡萄糖条件下，辛伐他汀剂量依赖性地抑制VSMC迁移，PI3K / Akt通路活性降低，c-Raf和Ras表达降低，RhoB升高但RhoA，Rac1和Cdc2表达却不升高，剂量依赖性地抑制MMP-2，但不是MMP-9，活性和剂量依赖性地抑制NF-κB活性。结论：在高葡萄糖条件下抑制VSMC迁移的途径有两种。第一条途径与甲羟戊酸有关，但与RhoA蛋白无关，涉及抑制Ras和PI3K / Akt信号。第二种途径与甲羟戊酸不相关，涉及直接增加RhoB表达。

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