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Journal of Lipid Research, Vol. 49, 521-530, March 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Angiotensin II increases vascular proteoglycan content preceding and contributing to atherosclerosis development¹

Fei Huang^*, Joel C. Thompson^*, Patricia G. Wilson^*, Hnin H. Aung, John C. Rutledge and Lisa R. Tannock^2,*,

^* Division of Endocrinology and Metabolism, University of Kentucky, Lexington, KY 40536-0200
Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, University of California, Davis, Davis, CA 95616
Department of Veterans Affairs Medical Center, Lexington, KY 40511

¹ This work was presented in part at the Arteriosclerosis, Thrombosis, and Vascular Biology annual conference, Denver, CO, 2006.

Published, JLR Papers in Press, November 21, 2007.

² To whom correspondence should be addressed. e-mail: lisa.tannock{at}uky.edu

Angiotensin II (angII) is known to promote atherosclerosis; however, the mechanisms involved are not fully understood. To determine whether angII stimulates proteoglycan production and LDL retention, LDL receptor-deficient mice were infused with angII (1,000 ng/kg/min) or saline via osmotic minipumps. To control for the hypertensive effect of angII, a parallel group received norepinephrine (NE; 5.6 mg/kg/day). Arterial lipid accumulation was evaluated by measuring the retention rate of LDL in isolated carotid arteries perfused ex vivo. Mice infused with angII had increased vascular content of biglycan and perlecan and retained twice as much LDL as saline- or NE-infused mice, although no group developed atherosclerosis at this time. To determine whether this increase in biglycan and perlecan content predisposed to atherosclerosis development, mice were infused with angII, saline, or NE for 4 weeks, then pumps were removed and mice received an atherogenic Western diet for another 6 weeks. Mice that had received angII infusions had 3-fold increased atherosclerosis compared with mice that had received saline or NE, and apolipoprotein B colocalized with both proteoglycans. Thus, one mechanism by which angII promotes atherosclerosis is increased proteoglycan synthesis and increased arterial LDL retention, which precedes and contributes to atherosclerosis development.

Supplementary key words low density lipoprotein retention • biglycan • extracellular matrix • norepinephrine