Angiotensin II Induces Vascular Cell Adhesion Molecule-1 Expression In Rat Vasculature

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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-κB-like binding activity and transactivated an NF-κB–driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-κB activation and VCAM-1 mRNA accumulation. IκB-α 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-κB-like transcriptional mechanisms.