This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Nagashima, H. Articles by Kasanuki, H. Search for Related Content PubMed PubMed Citation Articles by Nagashima, H. Articles by Kasanuki, H. Related Collections Apoptosis

(Circulation. 2001;104:I-282.)
© 2001 American Heart Association, Inc.

Aortic and Peripheral Vascular Surgery

Angiotensin II Type 2 Receptor Mediates Vascular Smooth Muscle Cell Apoptosis in Cystic Medial Degeneration Associated With Marfan’s Syndrome

Hirotaka Nagashima, MD, PhD; Yasunari Sakomura, MD, PhD; Yoshikazu Aoka, MD; Kenta Uto, MD; Kin-ichi Kameyama, MD; Motoko Ogawa, MD; Shigeyuki Aomi, MD, PhD; Hitoshi Koyanagi, MD, PhD; Naoko Ishizuka, MD, PhD; Mitsuhide Naruse, MD, PhD; Masatoshi Kawana, MD, PhD; Hiroshi Kasanuki, MD, PhD

From the Departments of Cardiology (H.N., Y.S., Y.A., K.U., K.K., M.O., N.I., M.K., H. Kasanuki) and Cardiovascular Surgery (S.A., H. Koyanagi), The Heart Institute of Japan, and the Second Department of Medicine (M.N.), Tokyo Women’s Medical University, Tokyo, Japan.

Reprint requests to Hirotaka Nagashima, MD, PhD, Department of Cardiology, The Heart Institute of Japan, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjyuku-ku, Tokyo162-8666, Japan. E-mail mnagasih{at}hij.twmu.ac.jp

Background— Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan’s syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R).

Methods and Results— To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients.

Conclusions— Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.

Key Words: angiotensin • receptors • apoptosis • muscle, smooth • aorta