Angiotensin inhibition decreases progression of advanced atherosclerosis and stabilizes established atherosclerotic plaques.

Suganuma E, Babaev VR, Motojima M, Zuo Y, Ayabe N, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V
J Am Soc Nephrol. 2007 18 (8): 2311-9

PMID: 17634441 · DOI:10.1681/ASN.2006090967

Although increased extracellular matrix (ECM) is pathogenic in a variety of chronic tissue injuries, reduced and/or disrupted ECM may be detrimental in atherosclerosis and rather destabilize existing atherosclerotic lesions. This study therefore assessed the effects of angiotensin II (AngII) antagonism on ECM components of advanced atherosclerosis. Twenty-four-week-old apolipoprotein E-deficient mice were treated with the AngII antagonist losartan for 12 wk. Controls received water or hydralazine. AngII antagonism significantly reduced progression of established atherosclerosis, whereas hydralazine showed no benefit despite similar decrease in BP. Although there was no difference in the macrophage component, AngII antagonism increased the relative collagen portion of the lesions; lessened elastin fragmentation, increased the total elastin content of the aorta; and reduced the mRNA and activity/protein of the elastolytic proteases, cathepsin S, and metalloproteinase-9. Extracellular elastin degradation by cultured smooth muscle cells (SMC) was reduced by losartan, as was SMC invasion through an elastin gel barrier. Thus, AngII antagonism lessens progression of atherosclerosis, increases collagen, and preserves elastin components of ECM within the vascular lesions, which, at least in part, is modulated by effects on SMC. These effects not only decrease further expansion of advanced lesions but also stabilize the established atherosclerotic plaques and may underlie the decreased incidence of acute cardiovascular events that are observed in patients in whom AngII antagonism is begun after atherosclerosis is already established.

MeSH Terms (19)

Angiotensin II Angiotensin II Type 1 Receptor Blockers Animals Antihypertensive Agents Aortic Diseases Apolipoproteins E Atherosclerosis Blood Pressure Body Weight Disease Progression Elasticity Female Hydralazine Lipids Losartan Mice Mice, Inbred C57BL Mice, Mutant Strains Vasoconstrictor Agents

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