Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature - A potential link between the renin-angiotensin system and atherosclerosis
Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature - A potential link between the renin-angiotensin system and atherosclerosis
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DOI：
10.1161/01.cir.100.11.1223
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发表时间：
1999-09-14
期刊：
影响因子：
37.8
通讯作者：
Medford, RM
中科院分区：
文献类型：
--
作者：
Tummala, PE;Chen, XL;Medford, RM
背景-肾素-血管紧张素系统激活的高血压患者可能更频繁地发生心血管缺血事件。我们验证了血管紧张素II(Ang II)可能通过增加血管细胞黏附分子-1(VCAM-1)等血管炎症基因的表达而参与动脉粥样硬化的假说。方法和结果：去甲肾上腺素或Ang II灌流6天后，大鼠表现出类似的高血压反应，但只有Ang II处理的大鼠主动脉VCAM-1蛋白和mRNA的表达显著增加。口服氯沙坦治疗(50毫克。Kg(-1)。D(-1)抑制Ang II诱导的高血压和主动脉VCAM-1mRNA的表达。血管紧张素转换酶II显著增加培养的大鼠主动脉平滑肌细胞VCAM-1mRNA的表达。Ang II还诱导核因子-kappa B样结合活性，反式激活由核因子-kappaB驱动的VCAM-1启动子。氯沙坦和蛋白酶体抑制剂阻断血管紧张素转换酶II诱导的核因子-kappaB的激活和VCAM-1mRNA的积聚，IkB-α过表达抑制血管紧张素转换酶Ⅱ诱导的血管细胞黏附分子-1启动子的反式激活。结论血管紧张素转换酶Ⅱ可能通过蛋白酶体依赖的类核因子-kappaB转录机制激活血管细胞黏附分子1，从而参与动脉粥样硬化的形成。
Background-Cardiovascular ischemic events may occur more frequently in hypertensive patients with activated renin-angiotensin systems. We tested the hypothesis that angiotensin II: (Ang II) may contribute to atherosclerosis by increasing expression of vascular inflammatory genes such as Vascular cell adhesion molecule-1 (VCAM-1).Methods and Results-Rats infused with norepinephrine or Ang II for 6 days developed similar hypertensive responses, but only Ang II-treated rats exhibited significant increases in aortic VCAM-1 protein and mRNA expression. Oral losartan treatment (50 mg . Kg(-1). d(-1)) inhibited Ang II-induced hypertension and aortic VCAM-1 mRNA expression. Ang II treatment significantly increased VCAM-1 mRNA expression in cultured rat aortic smooth muscle cells (RASMCs). Ang II also induced nuclear NF-kappa B-like binding activity and transactivated an NF-kappa B-driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-kappa B activation and VCAM-1 mRNA accumulation, IKB-alpha overexpression in RASMCs inhibited Ang II-induced VCAM-1 promoter transactivation.Conclusion-Ang II may contribute to atherogenesis by activation of VCAM-1 through proteasome dependent, NF-kappa B-like transcriptional mechanisms.