Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia

Giangrande, Paloma H., Zhang, JianXin, Tanner, Alice, Eckhart, Andrea D., Rempel, Rachel E., Andrechek, Eran R., Layzer, Juliana M., Keys, Janelle R., Hagen, Per-Otto, Nevins, Joseph R., Koch, Walter J. and Sullenger, Bruce A. (2007) Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia. Proceedings of the National Academy of Sciences of the United States of America, 104 32: 12988-12993. doi:10.1073/pnas.0704754104


Author Giangrande, Paloma H.
Zhang, JianXin
Tanner, Alice
Eckhart, Andrea D.
Rempel, Rachel E.
Andrechek, Eran R.
Layzer, Juliana M.
Keys, Janelle R.
Hagen, Per-Otto
Nevins, Joseph R.
Koch, Walter J.
Sullenger, Bruce A.
Title Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2007-08-07
Year available 2007
Sub-type Article (original research)
DOI 10.1073/pnas.0704754104
Open Access Status Not Open Access
Volume 104
Issue 32
Start page 12988
End page 12993
Total pages 6
Place of publication United States
Publisher National Academy of Sciences of the U.S.
Language eng
Subject 110202 Haematology
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
Abstract Intimal hyperplasia (IH) and restenosis limit the long-term utility of bypass surgery and angioplasty due to pathological proliferation and migration of vascular smooth muscle cells (VSMCs) into the intima of treated vessels. Consequently, much attention has been focused on developing inhibitory agents that reduce this pathogenic process. The E2F transcription factors are key cell cycle regulators that play important roles in modulating cell proliferation and cell fate. Nonselective E2F inhibitors have thus been extensively evaluated for this purpose. Surprisingly, these E2F inhibitors have failed to reduce IH. These findings prompted us to evaluate the roles of different E2Fs during IH to determine how selective targeting of E2F isoforms impacts VSMC proliferation. Importantly, we show that E2F3 promotes proliferation of VSMCs leading to increased IH, whereas E2F4 inhibits this pathological response. Furthermore, we use RNA probes to show that selective inhibition of E2F3, not global inhibition of E2F activity, significantly reduces VSMC proliferation and limits IH in murine bypass grafts.
Keyword Cell Cycle
RNA therapeutics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Wed, 11 Feb 2009, 12:59:55 EST by Paul Rollo on behalf of Institute for Molecular Bioscience