Details

Autor(en) / Beteiligte

• TUMMALA, P. E
• CHEN, X.-L
• SUNDELL, C. L
• LAURSEN, J. B
• HAMMES, C. P
• ALEXANDER, R. W
• HARRISON, D. G
• MEDFORD, R. M

Titel

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

Ist Teil von

• Circulation (New York, N.Y.), 1999-09, Vol.100 (11), p.1223-1229

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

1999

Quelle

MEDLINE

Beschreibungen/Notizen

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