Angiotensin II amplifies macrophage-driven atherosclerosis

Arteriosclerosis, Thrombosis, and Vascular Biology
Ayabe NobuhikoValentina Kon

Abstract

We evaluated the role of angiotensin II (AII) in a marrow-derived macrophage-driven model of atherosclerosis. Eight-week-old C57BL/6 wild-type mice were reconstituted with bone marrow harvested from apolipoprotein E-deficient (apoE-/---> apoE+/+) or wild-type for apoE gene (apoE+/+--> apoE+/+) mice. At 20 weeks, mice were exposed to either AII (1000 ng/kg per minute subcutaneously) or saline for 2 weeks. Animals did not differ in body weight, blood pressure, cholesterol/triglycerides, or peripheral blood monocyte counts. ApoE-/---> apoE+/+ mice exposed to AII had 3-fold greater atherosclerotic area than saline-treated apoE-/---> apoE+/+ mice. By contrast, AII did not affect atherosclerosis in apoE+/+--> apoE+/+ mice. Macrophage-positive areas were increased by AII in mice reconstituted with either apoE-deficient or apoE-competent marrow. AII also significantly increased fragmentation of elastin laminae in both apoE-/---> apoE+/+ and apoE+/+--> apoE+/+ mice. In vitro, AII caused greater increase in monocyte chemoattractant protein-1-stimulated migration of macrophages harvested from AII-infused versus saline-infused mice. The current studies reveal that AII has both initiating and sustaining proatherogenic effects. By promoting ...Continue Reading

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Citations

Apr 29, 2010·Current Atherosclerosis Reports·Yi-Xin Jim WangBruce Hammock
Nov 26, 2010·Nature Reviews. Nephrology·Valentina KonSergio Fazio
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