doi: 10.1161/01.CIR.0000151787.39451.BC
(Circulation. 2004;110:3749-3752.)
© 2004 American Heart Association, Inc.
Editorial |
Unexpected Proatherogenic Properties of p21
Beyond Cell Cycle Control?
From the Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia-CSIC, Valencia, Spain.
Correspondence to Vicente Andrés, PhD, Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia-CSIC, 46010 Valencia, Spain. E-mail vandres@ibv.csic.es
Key Words: Editorials • apoptosis • atherosclerosis • cell cycle • inflammation
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Atherosclerosis is an inflammatory disease that involves the interplay between endothelial cells, smooth muscle cells (SMCs), and immune cells.1,2 Various atherogenic stimuli lead to endothelial damage, which in turn triggers the adhesion and extravasation of circulating monocytes and lymphocytes into the artery wall. Resident immune cells produce a plethora of inflammatory mediators that exacerbate leukocyte recruitment and proliferation and promote SMC growth and migration from the underlying media toward the developing atheroma. Abnormal cell proliferation and migration are also a hallmark of neointimal thickening during postangioplasty restenosis, transplant vasculopathy, and graft atherosclerosis.1,3
See p 3830
Mammalian cell cycle progression is governed by the concerted activation of holoenzymes composed of a catalytic cyclin-dependent protein kinase (CDK) and a regulatory subunit named cyclin. Cell proliferation is constrained by the interaction of CDK/cyclin holoenzymes with members of the Cip/Kip (for CDK interacting protein/kinase inhibitory protein) and Ink4 (for inhibitor of CDK4) families of CDK inhibitory proteins (CKIs).4 Ink4 proteins (p16Ink4a, p15Ink4b, p18Ink4c, p19Ink4d) are thought to be specific for cyclin D–associated CDKs, whereas Cip/Kip proteins (p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2) bind to and inhibit a wide spectrum of CDK/cyclin complexes.
Role of Cell Cycle–Regulatory Factors in Neointimal Thickening: Lessons Learned From Animal Models
There is compelling evidence from animal studies that cell cycle–regulatory factors are key modulators of neointimal lesion development, at least in part through their ability to regulate cell proliferation and locomotion.5,6 First, intraluminal delivery of antisense oligonucleotides against several CDKs and cyclins or pharmacological inhibition of CDK activity efficiently reduced neointimal thickening after balloon angioplasty and vascular grafting.
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Circulation 2004 110: 3830-3841.
Circulation 2004 110: 3830-3841.
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