血管紧张素II诱导大鼠血管中血管细胞黏附分子-1的表达：肾素-血管紧张素系统与动脉粥样硬化之间的潜在联系。

Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis.

作者信息

Tummala P E, Chen X L, Sundell C L, Laursen J B, Hammes C P, Alexander R W, Harrison D G, Medford R M

机构信息

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.

出版信息

Circulation. 1999 Sep 14;100(11):1223-9. doi: 10.1161/01.cir.100.11.1223.

DOI:10.1161/01.cir.100.11.1223

PMID:10484544

Abstract

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-kappaB-like binding activity and transactivated an NF-kappaB-driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-kappaB activation and VCAM-1 mRNA accumulation. IkappaB-alpha overexpression in RASMCs inhibited Ang II-induced VCAM-1 promoter transactivation.

CONCLUSIONS

Ang II may contribute to atherogenesis by activation of VCAM-1 through proteasome dependent, NF-kappaB-like transcriptional mechanisms.

摘要

背景

在肾素 - 血管紧张素系统激活的高血压患者中，心血管缺血事件可能更频繁地发生。我们检验了血管紧张素II（Ang II）可能通过增加血管炎症基因如血管细胞黏附分子-1（VCAM-1）的表达来促进动脉粥样硬化的假说。

方法与结果

用去甲肾上腺素或Ang II灌注6天的大鼠出现相似的高血压反应，但只有接受Ang II治疗的大鼠主动脉VCAM-1蛋白和mRNA表达显著增加。口服氯沙坦治疗（50 mg·kg⁻¹·d⁻¹）可抑制Ang II诱导的高血压和主动脉VCAM-1 mRNA表达。Ang II处理显著增加培养的大鼠主动脉平滑肌细胞（RASMCs）中VCAM-1 mRNA的表达。Ang II还诱导核NF-κB样结合活性并反式激活NF-κB驱动的VCAM-1启动子。氯沙坦和蛋白酶体抑制剂可阻断Ang II诱导的NF-κB激活和VCAM-1 mRNA积累。RASMCs中IkappaB-α的过表达抑制了Ang II诱导的VCAM-1启动子反式激活。