This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/7/1257    most recent ATVBAHA.108.165688v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hou, Y. Articles by Matsuo, O. Search for Related Content PubMed PubMed Citation Articles by Hou, Y. Articles by Matsuo, O.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1257.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Alpha2-Antiplasmin Is a Critical Regulator of Angiotensin II–Mediated Vascular Remodeling

YongZhong Hou; Kiyotaka Okada; Chikako Okamoto; Shigeru Ueshima; Osamu Matsuo

From the Department of Physiology (Y.Z.H., K.O., C.O., O.M.), Kinki University School of Medicine, Osaka, Japan; and the Department of Food Science and Nutrition (S.U.), Kinki University School of Agriculture, Nara, Japan; and the Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

Osamu Matsuo and Yongzhong Hou, Department of Physiology, Kinki University School of Medicine, Osaka, Japan; and the Department of Food, Science and Nutrition (S.U.), Kinki University School of Agriculture, Nara, Japan. E-mail matsuo-o{at}med.kindai.ac.jp and hou_yz@yahoo.com

Objective— Alpha2-antiplasmin (2-AP) is the major circulating inhibitor of plasmin, which plays a determining role in the regulation of intravascular fibrinolysis. We investigated the role of ₂-AP on vascular remodeling in response to angiotensin II (Ang II).

Methods and Results— 2-AP–deficient mice were performed. Ang II and N-nitro- L-arginine methyl ester (L-NAME)–induced perivascular fibrosis was significantly decreased in 2-AP^–/– mice compared with wild-type mice. In situ gelatinolytic activity analysis shows that perivascular gelatinolytic activity was increased in 2-AP^–/– mice, which was responsible for decreased perivascular fibrosis in response to Ang II and L-NAME. Ang II–induced arterial wall thickening, vascular cell proliferation, apoptosis, c-Myc, and collagen I expression were significantly decreased in 2-AP^–/– mice compared with wild-type mice. Further analysis shows that increased p53 and p21 expression were responsible for inhibition of Ang II–induced vascular remodeling in 2-AP^–/– mice.

Conclusion— The results show that 2-AP is a critical regulator for vascular remodeling by inhibiting p53/p21 pathway, suggesting that 2-AP is proposed to be a potential therapeutic target for vascular remodeling.

2-AP is the major circulating inhibitor of plasmin. Here we reported that 2-AP^–/– suppressed Ang II and L-NAME–induced perivascular fibrosis by decreased collagen I expression. 2-AP^–/– decreased Ang II–induced vascular remodeling by inhibiting p53/p21 pathway, suggesting that 2-AP is proposed to be a potential therapeutic target for vascular remodeling.

Key Words: Ang II • L-NAME • alpha2-antiplasmin • vascular remodeling • perivascular fibrosis