Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury
2013
Hirata, Yoichiro | Kurobe, Hirotsugu | Nishio, Chika | Tanaka, Kimie | Fukuda, Daiju | Uematsu, Etsuko | Nishimoto, Sachiko | Soeki, Takeshi | Harada, Nagakatsu | Sakaue, Hiroshi | Kitagawa, Tetsuya | Shimabukuro, Michio | Nakaya, Yutaka | Sata, Masataka
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 24nmol/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.
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