title: Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury.
abstract: Exendin-4 is a glucagon-like peptide-1 receptor agonist that has been used as a drug for treatment of type 2 diabetes. To investigate the effect of exendin-4 on the cardiovascular system, we investigated the impact of exendin-4 on neointimal hyperplasia of the femoral artery after vascular injury. We performed wire-mediated endovascular injury in C57BL/6 mice, followed by administration of exendin-4 24 nmol/kg/day via infusion pump. Four weeks after the injury, exendin-4 treatment significantly attenuated neointimal hyperplasia of the injured artery, although it did not affect glucose metabolism and lipid profile in wild-type mice. Immunofluorescence study revealed abundant expression of GLP-1 receptor on α-smooth muscle actin-positive cells in the injured vessel. Cell proliferation assay using rat aortic smooth muscle cells showed that exendin-4 reduced PDGF-BB induced smooth muscle cell proliferation through the cAMP/PKA pathway. Exendin-4 also inhibited TNFα production by peritoneal macrophages in response to inflammatory stimulus. Our findings indicate that a GLP-1 receptor agonist attenuated neointimal formation after vascular injury. GLP-1 receptor agonists or drugs that raise endogenous GLP-1 level might be effective in the treatment of vascular diseases.
authors.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.forename: Chika
authors.initials: C
authors.lastname: Nishio
authors.forename: Kimie
authors.initials: K
authors.lastname: Tanaka
authors.forename: Daiju
authors.initials: D
authors.lastname: Fukuda
authors.forename: Etsuko
authors.initials: E
authors.lastname: Uematsu
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nishimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Michio
authors.initials: M
authors.lastname: Shimabukuro
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000077270:Exenatide; D005263:Femoral Artery / Q000293:injuries; D005455:Fluorescent Antibody Technique; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007260:Infusion Pumps; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D058426:Neointima / Q000188:drug therapy* / Q000209:etiology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists* / Q000235:genetics; D057772:Vascular System Injuries / Q000150:complications / Q000188:drug therapy*; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000199:Actins; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C544013:alpha-smooth muscle actin, mouse; D000077270:Exenatide