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(Circulation Research. 2006;98:1113.)
© 2006 American Heart Association, Inc.

Editorials

Closing the Cycle

Skp2 Modulates Cyclic Nucleotides Antiproliferative Effects

Massimo Chiariello, Giovanni Esposito

From the Division of Cardiology, Federico II University, Naples, Italy.

Correspondence to Massimo Chiariello, MD, Division of Cardiology, Federico II University, Via Pansini, 5-Ed. 2, 80131 Naples, Italy. E-mail massimo.chiariello@unina.it

See related article, pages 1141–1150

Key Words: cAMP • Skp2 • cell cycle • smooth muscle cell • restenosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Smooth muscle cell (SMC) accumulation in the arterial intima is a key event in restenosis after angioplasty and bypass surgery and in the development of atherosclerotic lesions.¹ Restenosis, which is defined as "the arterial healing response after injury incurred during transluminal coronary revascularization," has been the principal drawback of percutaneous coronary interventions (PCI) since their introduction. The accumulation of arterial SMCs is caused by a combination of proliferation and directed migration of arterial SMCs from the media into the intima. Both these activities can be induced by cytokines and growth factors produced within the arterial wall and circulating cells in response to the vascular injury. A commonly accepted model of the response to arterial injury suggests that growth factors are released after injury, thereby changing the composition of the extracellular matrix and triggering a proliferation and migration program. SMCs undergo a phenotypic modulation from a contractile to a synthetic phenotype (dedifferentiation), proliferate into the media, migrate from the media into the intima, and subsequently form the neointima.

SMC transition from G1 to Gs cell phase induces neointima formation and modulates the atherosclerotic growth. The cell cycle is regulated by the interaction of multiple proteins, including cyclins, cyclin-dependent kinases, and phosphatases. Molecular complexes containing CDKs, cyclins, proliferating cell nuclear antigen (PCNA), and several other proteins regulate the major cell cycle transition points at the G1/S and G2/M boundaries. In addition to p21 and PCNA, the CDK2/cyclin A kinase complex includes a 19-kDa protein (p19, or SKP1) and a 45-kDa protein (p45, . . . [Full Text of this Article]

Related Article:

Altered S-Phase Kinase-Associated Protein-2 Levels Are a Major Mediator of Cyclic Nucleotide–Induced Inhibition of Vascular Smooth Muscle Cell Proliferation

Yih-Jer Wu, Mark Bond, Graciela B. Sala-Newby, and Andrew C. Newby
Circ. Res. 2006 98: 1141-1150. [Abstract] [Full Text] [PDF]

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