title: Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury.
abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Goto
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomiyama
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mita
authors.forename: Eisuke
authors.initials: E
authors.lastname: Yasunari
authors.forename: Kosuke
authors.initials: K
authors.lastname: Azuma
authors.forename: Koji
authors.initials: K
authors.lastname: Komiya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Arakawa
authors.forename: Wen Long
authors.initials: WL
authors.lastname: Jin
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima / Q000517:prevention & control*; D010455:Peptides / Q000627:therapeutic use*; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists*; D015398:Signal Transduction; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology; D057772:Vascular System Injuries / Q000188:drug therapy* / Q000473:pathology; D014688:Venoms / Q000627:therapeutic use*
chemical_list: C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D005947:Glucose