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

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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
Externally publishedYes

Fingerprint

Apolipoproteins E
Angiotensin II
Atherosclerosis
Macrophages
Elastin
Bone Marrow
Tunica Intima
Chemokine CCL2

Keywords

  • Angiotensin II
  • Atherosclerosis
  • Macrophage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nobuhiko, A., Suganuma, E., Babaev, V. R., Fogo, A., Swift, L. L., Linton, M. F., ... 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

Angiotensin II amplifies macrophage-driven atherosclerosis. / Nobuhiko, Ayabe; Suganuma, Eisuke; Babaev, Vladimir R.; Fogo, Agnes; Swift, Larry L.; Linton, MacRae F.; Fazio, Sergio; Ichikawa, Iekuni; Kon, Valentina.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 24, No. 11, 11.2004, p. 2143-2148.

Research output: Contribution to journalArticle

Nobuhiko, A, Suganuma, E, Babaev, VR, Fogo, A, Swift, LL, Linton, MF, Fazio, S, Ichikawa, I & Kon, V 2004, 'Angiotensin II amplifies macrophage-driven atherosclerosis', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 11, pp. 2143-2148. https://doi.org/10.1161/01.ATV.0000145607.03879.e0
Nobuhiko, Ayabe ; Suganuma, Eisuke ; Babaev, Vladimir R. ; Fogo, Agnes ; Swift, Larry L. ; Linton, MacRae F. ; Fazio, Sergio ; Ichikawa, Iekuni ; Kon, Valentina. / Angiotensin II amplifies macrophage-driven atherosclerosis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2004 ; Vol. 24, No. 11. pp. 2143-2148.
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