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(Circulation. 2001;103:2879.)
© 2001 American Heart Association, Inc.

Editorial

Cell Cycle and Cell Migration

New Pieces to the Puzzle

Manfred Boehm, MD; Elizabeth G. Nabel, MD

From the Vascular Biology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to Elizabeth G. Nabel, MD, NHLBI/NIH, Bldg 10/8C 103, Bethesda, MD 20892. E-mail enabel@nih.gov

Key Words: Editorials • cell cycle • cyclins

Formation of a healed arterial wound is a landmark event during the repair of vascular lesions. Adult coronary, peripheral, and cerebral arteries are exposed to multiple stresses, including mechanical trauma, endothelial denudation, damage to intimal and medial smooth muscle, abnormal shear stresses, and oxidation of LDL by macrophages, and they must undergo repair. This wound repair process, like in many other organs, requires that a complex network of molecular signals be regulated within the cytoplasm and nucleus of an endothelial or smooth muscle cell. The cell cycle is a key regulator of these signals and has direct effects on multiple cell processes, including cell proliferation, DNA repair, apoptosis, and cell migration.

Vascular smooth muscle cells (VSMCs) within the media of adult arteries are normally quiescent, proliferate at low indices, and exist in the G₀ phase of the cell cycle (Figure 1). On stimulation by growth factors or after mechanical trauma, VSMCs exit the quiescent stage G₀ and progress through the G₁ and G₁/S transition of the cell cycle. G₁ progression is regulated by the assembly and phosphorylation of G₁ cyclin/cyclin-dependent kinase (CDK) complexes, predominantly cyclin D/CDK-4,6 and cyclin E/CDK-2 in VSMCs. For example, cyclin D is a growth factor sensor whose transcription initiation, assembly, and nuclear transport is mitogen-dependent. Endogenous inhibitors of the cyclin/CDK complexes are termed the CDK inhibitors (CKIs).¹ Two groups of CKIs are dominant in cardiovascular biology: the CIP/KIP family, which includes p21^Cip1, p27^Kip1, and p57^Kip2, and the INK4 family, which includes . . . [Full Text of this Article]

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