Angiotensin II amplifies macrophage-driven atherosclerosis.

Nobuhiko A, Suganuma E, Babaev VR, Fogo A, Swift LL, Linton MF, Fazio S, Ichikawa I, Kon V
Arterioscler Thromb Vasc Biol. 2004 24 (11): 2143-8

PMID: 15374850 · DOI:10.1161/01.ATV.0000145607.03879.e0

OBJECTIVE - We evaluated the role of angiotensin II (AII) in a marrow-derived macrophage-driven model of atherosclerosis.

METHODS AND RESULTS - 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.

CONCLUSIONS - The current studies reveal that AII has both initiating and sustaining proatherogenic effects. By promoting macrophage migration into the vascular intima, AII is pivotal in initiating atherosclerosis; by promoting elastin breaks, a novel mechanism implicated in migration and proliferation of smooth muscle cells, AII may be pivotal in subsequent development and expansion of atherosclerotic lesion.

MeSH Terms (14)

Angiotensin II Animals Apolipoproteins E Arteriosclerosis Bone Marrow Transplantation Cell Movement Cholesterol Disease Models, Animal Female Infusion Pumps, Implantable Macrophages Macrophages, Peritoneal Mice Mice, Inbred C57BL

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