Expression of Q227L-Gαs inhibits intimal vessel wall hyperplasia after balloon injury

Wilfred Holness, Tara A. Santore, George P. Brown, John T. Fallon, Mark B. Taubman, Ravi Iyengar

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Interaction between signaling pathways regulates many cellular functions, including proliferation. The Gαs/cAMP pathway is known to inhibit signal flow from receptor tyrosine kinases to mitogen-activated protein kinase (MAPK)-1,2 and, thus, inhibit proliferation. Elevation of cAMP or adenovirus-directed expression of mutant (Q227L)-Gαss*) inhibits the proliferation of rat vascular smooth muscle cells (VSMCs) in culture. Platelet-derived growth factor (PDGF) stimulated MAPK activation and DNA synthesis was also blocked by expression of αs*. However, it is not known whether such mechanisms are operative in vivo. Proliferation of vascular smooth muscle cells in vivo was induced by balloon injury of carotid arteries in the rat. Recombinant adenovirus encoding β-galactosidase (β-gal) or αs* was applied to arterial segments injured by the balloon catheters. The αs*-treated vessels showed decreased phospho-MAPK staining in the intima as compared with β-gal-treated vessels. Application of αs*, but not β-gal containing adenovirus, inhibited formation of neointima by 50%. No change was observed in total vessel diameter or in the media or adventitia. These results suggest that the interaction between the Gαs and MAPK pathways can regulate proliferation in vivo and that targeted expression of activated Gαs may have therapeutic potential for the treatment of vascular pathophysiologies that arise from intimal hyperplasia.

Original languageEnglish
Pages (from-to)1288-1293
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number3
DOIs
StatePublished - 30 Jan 2001

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