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: Yoichiro Hirata, Hirotsugu Kurobe, Chika Nishio, Kimie Tanaka, Daiju Fukuda, Etsuko Uematsu, Sachiko Nishimoto, Takeshi Soeki, Nagakatsu Harada, Hiroshi Sakaue, Tetsuya Kitagawa, Michio Shimabukuro, Yutaka Nakaya, Masataka Sata
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 699 Issue 1-3 Pg. 106-11 (Jan 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23220706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Actins
• Glp1r protein, mouse
• Glp1r protein, rat
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Peptides
• Receptors, Glucagon
• Venoms
• alpha-smooth muscle actin, mouse
• Exenatide

Topics

• Actins (metabolism)
• Animals
• Aorta (cytology, drug effects, metabolism)
• Cell Proliferation (drug effects)
• Exenatide
• Femoral Artery (injuries)
• Fluorescent Antibody Technique
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents (administration & dosage, pharmacology)
• Infusion Pumps
• Macrophages, Peritoneal (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (cytology, drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• Neointima (drug therapy, etiology)
• Peptides (administration & dosage, pharmacology)
• Rats
• Receptors, Glucagon (agonists, genetics)
• Vascular System Injuries (complications, drug therapy)
• Venoms (administration & dosage, pharmacology)