Angiotensin II induces histomorphologic features of unstable plaque in a murine model of accelerated atherosclerosis

Valdeci da Cunha, Baby Martin-McNulty, Jon Vincelette, David F. Choy, We Wei Li, Miriam Schroeder, Mithra Mahmoudi, Meredith Halks-Miller, Dennis W Wilson, Ronald Vergona, Mark E. Sullivan, Yi Xin (Jim) Wang

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background: We explored the role of angiotensin II in determining the histomorphometric features of plaque stability in apolipoprotein E-deficient mice submitted to ligation of the carotid artery. Methods: Six-month-old apolipoprotein E-deficient mice underwent ligation of the common left carotid artery and were immediately assigned to receive either angiotensin II (1.4 mg · kg-1 · d-1 subcutaneously) or vehicle (phosphate-buffered saline; control) via a subcutaneous osmotic minipump for 4 weeks. Results: Ligated arteries from control animals developed intimal lesions composed of macrophage foam cell plaques, which accumulated adjacent to the internal elastic lamina and were surrounded by a fibromuscular layer. Angiotensin II-treated mice had a greater intimal area (threefold), which was accompanied by a fivefold increase in the foam cell area. Lesions from angiotensin II-treated mice also displayed complex morphology characterized by intralesional neovasculature and hemorrhage. The content of active matrix metalloproteinase 2, mainly colocalized with macrophage foam cells, and the production of the inflammatory mediators monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 were also increased by angiotensin II treatment. Although angiotensin II induced vessel expansion and lumen loss to a similar extent, only vessel enlargement correlated with intimal area. Conclusions: Taken together, this study's results support a role of angiotensin II in plaque vulnerability by promoting intraplaque neovascularization/hemorrhage, inflammation, and expansive remodeling.

Original languageEnglish (US)
Pages (from-to)364-371
Number of pages8
JournalJournal of Vascular Surgery
Issue number2
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery


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