期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 699, 期 1-3, 页码 106-111出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.11.057
关键词
Exendin-4; GLP-1; Endovascular injury; Neointimal hyperplasia; Diabetes mellitus
资金
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health, Labor and Welfare of Japan
- Grants-in-Aid for Scientific Research [24659392, 25293184, 23591314, 21117007, 22390159, 25670390] Funding Source: KAKEN
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 wildtype mice. Immunofluorescence study revealed abundant expression of GLP-1 receptor on alpha-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 TNF alpha 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. (C) 2012 Elsevier B.V. All rights reserved.
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