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.