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).


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.
Tummala
P E
PE
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Chen
X L
XL
Sundell
C L
CL
Laursen
J B
JB
Hammes
C P
CP
Alexander
R W
RW
Harrison
D G
DG
Medford
R M
RM
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
D011945:Receptors, Angiotensin; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D009638:Norepinephrine