Role of the p21 cyclin-dependent kinase inhibitor in limiting intimal cell proliferation in response to arterial injury

Zhi Yong Yang, Robert D. Simari, Neil D. Perkins, Hong San, David Gordon, Gary J. Nabel, Elizabeth G. Nabel

Research output: Contribution to journalArticle

202 Scopus citations

Abstract

Arterial injury induces a series of proliferative, vasoactive, and inflammatory responses that lead to vascular proliferative diseases, including atherosclerosis and restenosis. Although several factors have been defined which stimulate this process in vivo, the role of specific cellular gene products in limiting this response is not well understood. The p21 cyclin-dependent kinase inhibitor affects cell cycle progression, senescence, and differentiation in transformed cells, but its expression in injured blood vessels has not been investigated. In this study, we report that p21 protein is induced in porcine arteries following balloon catheter injury and suggest that p21 is likely to play a role in limiting arterial cell proliferation in vivo. Vascular endothelial and smooth muscle cell growth was arrested through the ability of p21 to inhibit progression through the G1 phase of the cell cycle. Following injury to porcine arteries, p21 gene product was detected in the neointima and correlated inversely with the location and kinetics of intimal cell proliferation. Direct gene transfer of p21 using an adenoviral vector into balloon injured porcine arteries inhibited the development of intimal hyperplasia. Taken together, these findings suggest that p21, and possibly related cyclin-dependent kinase inhibitors, may normally regulate cellular proliferation following arterial injury, and strategies to increase its expression may prove therapeutically beneficial in vascular diseases.

Original languageEnglish (US)
Pages (from-to)7905-7910
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number15
DOIs
StatePublished - Jul 23 1996

Keywords

  • cell cycle
  • cyclin
  • gene therapy
  • vascular smooth muscle cells

ASJC Scopus subject areas

  • General

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