This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Taylor, A. M. Articles by McNamara, C. A. Search for Related Content PubMed PubMed Citation Articles by Taylor, A. M. Articles by McNamara, C. A.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1717.)
© 2003 American Heart Association, Inc.

Editorials

Regulation of Vascular Smooth Muscle Cell Growth

Targeting the Final Common Pathway

Angela M. Taylor; Coleen A. McNamara

From the University of Virginia Health Sciences Center, Charlottesville, Va.

Correspondence to Coleen A. McNamara, University of Virginia, Box 801394 MR5, Charlottesville, VA 22908. E-mail cam8c@virginia.edu

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

Arterial injury initiates a complex series of events including proliferation of smooth muscle cells (SMCs) that culminates in the formation of the neointima. Neointimal formation can be a clinically problematic event, significantly narrowing the vessel lumen after angioplasty, bypass vein grafting, and transplant. Numerous growth factors and cytokines trigger the complex and redundant signaling pathways that lead to cell cycle entry.^1–6 Because of the redundancy of these signaling pathways, targeting individual growth factors and cytokines has failed to affect neointimal proliferation and has obviated the need to target the "final common pathway" of events.¹

See page 1788

Growth factor–stimulated proliferation is mediated by an early upregulation in transcription of the proto-oncogenes c-fos, c-myc, c-myb, B-myb, and ras.^1,7–10 The gene products then act as transcription factors that increase expression of cell cycle regulatory genes, including the cyclins, that when complexed with cyclin-dependent kinases (CDKs), coordinate cell cycle progression.^7,11–14 Certain proto-oncogene gene products also have the ability to augment cyclin-associated kinase activity and to couple growth regulatory signals to second messenger pathways.^15,16 Early upregulation of proliferating cell nuclear antigen (PCNA) occurs as well, stimulating DNA-polymerase- ability. In opposition to cell cycle progression are the cyclin-dependent kinase inhibitors (CKIs), such as p27^kip1 and p21^cip1. Transcription factors, such as p53, GAX, GATA-6, E2A, and Id, are expressed in the developing neointima after vascular injury and regulate the expression of the CKIs.^17–20 The final common pathway, therefore, involves regulation of the cell cycle through transcription and translation of cell cycle proteins. In addition, regulation . . . [Full Text of this Article]