This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Littlewood, T. D. Articles by Bennett, M. R. Search for Related Content PubMed PubMed Citation Articles by Littlewood, T. D. Articles by Bennett, M. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Related Article

(Circulation Research. 2007;100:302.)
© 2007 American Heart Association, Inc.

Editorials

Foxing Smooth Muscle Cells

FOXO3a–CYR61 Connection

Trevor D. Littlewood, Martin R. Bennett

From the Division of Cardiovascular Medicine (T.D.L., M.R.B.), Addenbrooke’s Hospital, Cambridge, UK.

Correspondence to Trevor D. Littlewood, the Division of Cardiovascular Medicine, Box 110, ACCI, Addenbrooke’s Hospital Cambridge, CB2 2QQ. E-mail +dl2@mole.bio.cam.ac.uk

See related article, pages 372–380

Key Words: FOXO3a • CYR61 • neointimal hyperplasia • vascular smooth muscle cell

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

Vascular smooth muscle cells (VSMCs) are essential for the structural integrity and contractile responses of the arterial vessel wall. VSMC proliferation and survival are also implicated in vascular disease including restenosis following angioplasty or stenting, and VSMC apoptosis is an important regulator of plaque stability. Thus, unraveling the molecular mechanisms that govern the survival, proliferation and migration of VSMCs is of great clinical importance. In this issue of Circulation Research Lee et al¹ have added another piece to this jigsaw puzzle. They show that the rapid increase in expression of the secreted cysteine-rich angiogenic protein CYR61 following stimulation of VSMCs with either serum growth factors or angiotensin II in vitro, or after mechanical arterial injury in vivo, can be attenuated by FOXO3a.

Previous studies have shown that CYR61 is highly expressed in human atherosclerotic plaques, correlating with the degree of stenosis and plaque histopathology.² Lee et al¹ investigated how expression of CYR61 is regulated. The CYR61 promoter contains multiple binding sites for different transcriptional regulators. In particular, Lee et al¹ identified a site for Forkhead/winged helix box gene, group O (FOXO) family of transcription factors. Because previous studies had indicated that FOXO3a inhibits neointimal hyperplasia by promoting cell cycle arrest and apoptosis,^3,4 Lee et al¹ investigated whether FOXO3a influenced the expression of CYR61. They demonstrate that FOXO3a functions as a transcriptional repressor of CYR61. Because the serine/threonine kinase Akt/PKB phosphorylates and inhibits FOXO3a activity, Lee et al¹ used a modified allele that contains mutated Akt phosphorylation . . . [Full Text of this Article]

Related Article:

Forkhead Transcription Factor FOXO3a Is a Negative Regulator of Angiogenic Immediate Early Gene CYR61, Leading to Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Hyperplasia

Hae-Young Lee, Jae-Woong Chung, Seock-Won Youn, Ju-Young Kim, Kyung-Woo Park, Bon-Kwon Koo, Byung-Hee Oh, Young-Bae Park, Brahim Chaqour, Kenneth Walsh, and Hyo-Soo Kim
Circ. Res. 2007 100: 372-380. [Abstract] [Full Text] [PDF]