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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:664.)
© 2004 American Heart Association, Inc.

Vascular Biology

Angiotensin II Type 1a Receptor Is Involved in Cell Infiltration, Cytokine Production, and Neovascularization in Infarcted Myocardium

Haruhiro Toko; Yunzeng Zou; Tohru Minamino; Masaya Sakamoto; Masanori Sano; Mutsuo Harada; Toshio Nagai; Takeshi Sugaya; Fumio Terasaki; Yasushi Kitaura; Issei Komuro

From the Department of Cardiovascular Science and Medicine (H.T., Y.Z., T.M., M. Sakamoto, M. Sano, M.H., T.N., I.K.), Chiba University Graduate School of Medicine, Chiba, Japan; Discovery Laboratory (T.S.), Tanabe Seiyaku Co, Ltd, Osaka, Japan; and Third Department of Internal Medicine (F.T., Y.K.), Osaka Medical College, Osaka, Japan.

Correspondence to Dr Issei Komuro, Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail komuro-tky{at}umin.ac.jp

Objective— Angiotensin II is critically involved in left ventricular remodeling after myocardial infarction. Neovascularization has been thought to prevent the development of left ventricular remodeling and deterioration to heart failure. To elucidate the role of angiotensin II in neovascularization during cardiac remodeling, we induced myocardial infarction in angiotensin II type1a receptor (AT1) knockout (KO) mice.

Methods and Results— There were more vessels in the border zone of infarcted hearts of wild-type (WT) mice and AT1KO mice at 14 days after operation, compared with in the left ventricle of sham-operated mice, and the number was larger in WT mice than in AT1KO mice. Consistent with these observations, the infarcted heart of AT1KO mice expressed lower levels of matrix metalloproteinase and endothelial nitric oxide synthase activity. More inflammatory cells such as granulocytes and macrophages were infiltrated in the infarcted hearts of WT mice than AT1KO mice at 4 days. A variety of cytokines and chemokines were increased in infarcted hearts of WT and AT1KO mice, and many of them were more remarkable in WT mice than in AT1KO mice at 14 days.

Conclusions— AT1 plays a critical role in inflammatory cell infiltration, cytokine production, and neovascularization in infarcted hearts.

Key Words: angiotensin II • AT1 receptor • neovascularization • myocardial infarction • cardiac remodeling

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