doi: 10.1161/CIRCRESAHA.108.188003
© 2008 American Heart Association, Inc.
Editorials |
Pathways of Proliferation
New Targets to Inhibit the Growth of Vascular Smooth Muscle Cells
From the Section of Cardiology, Department of Medicine, University of Chicago, Ill.
Correspondence to Stephen L. Archer, MD, FAHA, FACC, FRCP(C), Harold Hines Jr. Professor of Medicine, Chief of Cardiology, University of Chicago (MC6080), 5841 S Maryland Ave, Chicago, IL, 60637. E-mail sarcher@medicine.bsd.uchicago.edu
See related article, pages 1155–1163
Key Words: histone deacetylase • PPAR
• telomerase • coronary artery restenosis • pulmonary arterial hypertension
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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Excessive proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of many cardiovascular diseases, including atherosclerosis and pulmonary arterial hypertension (PAH). VSMC proliferation also underlies the failure of many therapies, notable examples being restenosis following coronary angioplasty, vein graft failure in patients with coronary artery bypass grafts, and transplant vasculopathy. Few therapies directly target excess VSMC proliferation, in part, because the underlying pathways have been unknown. Recently, several pathways of VSMC proliferation have been defined, and new therapeutic targets have emerged.
An example of the power of preventing VSMC proliferation in reducing human cardiovascular disease is the rapamycin (sirolimus)-coated coronary stent. After dozens of agents failed to prevent the 30% restenosis rate postangioplasty, this VSMC proliferation inhibitor reduced the number to 
6%.1 However, rapamycin has toxicities, limiting its systemic use. Moreover, the mechanisms of accelerated VSMC proliferation may vary by disease, and, thus, the efficacy of an antiproliferative drug will likely be contextual (ie, disease dependent). Understanding the pathways controlling proliferation offers hope for identifying drugs that selectively target proliferating cells. The contribution by Gizard et al in this issue of Circulation Research identifies such a pathway and suggests new therapeutic targets.2
Members of this group expand on their previous work showing that peroxisome proliferator-activated receptor (PPAR) activation suppresses G1
S cell cycle progression by increasing the expression of the cyclin dependent kinase (CDK) inhibitor p16INK4a.3
The present study is built on a solid body of knowledge of the cell cycle. Although growth factors are necessary to
Related Article:
/p16INK4a Pathway Inhibits Vascular Smooth Muscle Cell Proliferation by Repressing Cell Cycle–Dependent Telomerase Activation
Circ. Res. 2008 103: 1155-1163.