This Article Full Text Full Text (PDF) All Versions of this Article: 45/4/552    most recent 01.HYP.0000158263.64320.ebv1 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, M.-J. Articles by Lee, I.-K. Search for Related Content PubMed PubMed Citation Articles by Kim, M.-J. Articles by Lee, I.-K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Type 2 diabetes Smooth muscle proliferation and differentiation

(Hypertension. 2005;45:552.)
© 2005 American Heart Association, Inc.

Original Articles

Cilostazol Inhibits Vascular Smooth Muscle Cell Growth by Downregulation of the Transcription Factor E2F

Mi-Jung Kim; Keun-Gyu Park; Kyeong-Min Lee; Hye-Soon Kim; So-Yeon Kim; Chun-Soo Kim; Sang-Lak Lee; Young-Chae Chang; Joong-Yeol Park; Ki-Up Lee; In-Kyu Lee

From the Departments of Internal Medicine (M.-J.K., K.-G.P., K.-M.L., H.-S.K., I.-K.L.) and Institute for Medical Science, Physiology (S.-Y.K.), and Pediatrics (C.-S.K., S.-L.L.), Keimyung University School of Medicine, Daegu; Department of Pathology (Y.-C.C.), Catholic University of Daegu, School of Medicine, Daegu; and the Department of Internal Medicine (J.-Y.P., K.-I.U.), University of Ulsan College of Medicine, Seoul, Korea.

Correspondence to In-Kyu Lee, MD, PhD, Department of Internal Medicine, Keimyung University School of Medicine, 194 Dongsan-dong, Jung-gu, Daegu, 700-712, South Korea. E-mail inkyulee{at}dsmc.or.kr

Neointimal formation, the leading cause of restenosis, is caused by proliferation of vascular smooth muscle cells (VSMCs). Patients with diabetes mellitus have higher restenosis rates after coronary angioplasty than nondiabetic patients. Cilostazol, a selective type 3 phosphodiesterase inhibitor, is currently used to treat patients with diabetic vascular complications. Cilostazol is a potent antiplatelet agent that inhibits VSMC proliferation. In the present study, we examine whether the antiproliferative effect of cilostazol on VSMCs is mediated by inhibition of an important cell cycle transcription factor, E2F. Cilostazol inhibited the proliferation of human VSMCs in response to high glucose in vitro and virtually abolished neointimal formation in rats subjected to carotid artery injury in vivo. Moreover, the compound suppressed high-glucose–induced E2F–DNA binding activity, and the expression of E2F1, E2F2, cyclin A, and PCNA proteins. These data suggest that the beneficial effects of cilostazol on high-glucose–stimulated proliferation of VSMCs are mediated by the downregulation of E2F activity and expression of its downstream target genes, including E2F1, E2F2, cyclin A, and PCNA.

Key Words: diabetes mellitus • hyperplasia • vascular smooth muscle cells

This article has been cited by other articles:

				F. Zhou, L. Zhang, A. Wang, B. Song, K. Gong, L. Zhang, M. Hu, X. Zhang, N. Zhao, and Y. Gong The Association of GSK3{beta} with E2F1 Facilitates Nerve Growth Factor-induced Neural Cell Differentiation J. Biol. Chem., May 23, 2008; 283(21): 14506 - 14515. [Abstract] [Full Text] [PDF]

				H. Zhao, J. Quilley, D. C. Montrose, S. Rajagopalan, Q. Guan, and C. J. Smith Differential effects of phosphodiesterase PDE-3/PDE-4-specific inhibitors on vasoconstriction and cAMP-dependent vasorelaxation following balloon angioplasty Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2973 - H2981. [Abstract] [Full Text] [PDF]

				A. Schomig, A. Kastrati, and R. Wessely Prevention of Restenosis by Systemic Drug Therapy: Back to the Future? Circulation, November 1, 2005; 112(18): 2759 - 2761. [Full Text] [PDF]