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

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.