Angiotensin II amplifies macrophage-driven atherosclerosis

Ayabe Nobuhiko, Eisuke Suganuma, Vladimir R. Babaev, Agnes Fogo, Larry L. Swift, MacRae F. Linton, Sergio Fazio, Iekuni Ichikawa, Valentina Kon

    Research output: Contribution to journalArticle

    47 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)2143-2148
    Number of pages6
    JournalArteriosclerosis, thrombosis, and vascular biology
    Volume24
    Issue number11
    DOIs
    StatePublished - Nov 2004

    Keywords

    • Angiotensin II
    • Atherosclerosis
    • Macrophage

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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  • Cite this

    Nobuhiko, A., Suganuma, E., Babaev, V. R., Fogo, A., Swift, L. L., Linton, M. F., Fazio, S., Ichikawa, I., & Kon, V. (2004). Angiotensin II amplifies macrophage-driven atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology, 24(11), 2143-2148. https://doi.org/10.1161/01.ATV.0000145607.03879.e0