{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:56:21Z","timestamp":1781103381470,"version":"3.54.1"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,3,30]]},"abstract":"<jats:p>\n                    Restenosis continues to be a major problem limiting the effectiveness of revascularization procedures. To date, the roles of heterotrimeric G proteins in the triggering of pathological vascular smooth muscle (VSM) cell proliferation have not been elucidated. \u03b2\u03b3 subunits of heterotrimeric G proteins (G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    ) are known to activate mitogen-activated protein (MAP) kinases after stimulation of certain G protein-coupled receptors; however, their relevance in VSM mitogenesis\n                    <jats:italic>in vitro<\/jats:italic>\n                    or\n                    <jats:italic>in vivo<\/jats:italic>\n                    is not known. Using adenoviral-mediated transfer of a transgene encoding a peptide inhibitor of G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    signaling (\u03b2ARKct), we evaluated the role of G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    in MAP kinase activation and proliferation in response to several mitogens, including serum, in cultured rat VSM cells. Our results include the striking finding that serum-induced proliferation of VSM cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    is mediated largely via G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    . Furthermore, we studied the effects of\n                    <jats:italic>in vivo<\/jats:italic>\n                    adenoviral-mediated \u03b2ARKct gene transfer on VSM intimal hyperplasia in a rat carotid artery restenosis model. Our\n                    <jats:italic>in vivo<\/jats:italic>\n                    results demonstrated that the presence of the \u03b2ARKct in injured rat carotid arteries significantly reduced VSM intimal hyperplasia by 70%. Thus, G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    plays a critical role in physiological VSM proliferation, and targeted G\n                    <jats:sub>\u03b2\u03b3<\/jats:sub>\n                    inhibition represents a novel approach for the treatment of pathological conditions such as restenosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.7.3945","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"3945-3950","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":69,"title":["Targeting G\n                    <sub>\u03b2\u03b3<\/sub>\n                    signaling in arterial vascular smooth muscle proliferation: A novel strategy to limit restenosis"],"prefix":"10.1073","volume":"96","author":[{"given":"Guido","family":"Iaccarino","sequence":"first","affiliation":[{"name":"Departments of Surgery, Pharmacology and Cancer Biology, and Medicine and Biochemistry, and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Ashley","family":"Smithwick","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pharmacology and Cancer Biology, and Medicine and Biochemistry, and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pharmacology and Cancer Biology, and Medicine and Biochemistry, and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Pharmacology and Cancer Biology, and Medicine and Biochemistry, and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 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