Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury
Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury
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DOI：
10.1016/j.ejphar.2012.11.057
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发表时间：
2013-01-15
影响因子：
5
通讯作者：
Sata, Masataka
中科院分区：
文献类型：
--
作者：
Hirata, Yoichiro;Kurobe, Hirotsugu;Sata, Masataka
Exendin-4是一种胰高血糖素样肽-1受体激动剂，已被用作治疗2型糖尿病的药物。为了研究exendin-4对心血管系统的作用，我们研究了exendin-4对血管损伤后股动脉新生内膜增生的影响。我们在C57 BL/6小鼠中进行了导丝介导的血管内损伤，随后通过输注泵给予exendin-4 24 nmol/kg/天。损伤后4周，exendin-4治疗显著减弱了损伤动脉的新生内膜增生，尽管它不影响野生型小鼠的葡萄糖代谢和脂质谱。免疫荧光研究显示，GLP-1受体在受损血管中的α-平滑肌肌动蛋白阳性细胞上大量表达。用大鼠主动脉平滑肌细胞进行的细胞增殖试验表明，exendin-4通过cAMP/PKA途径减少PDGF-BB诱导的平滑肌细胞增殖。毒蜥外泌肽-4还抑制响应于炎症刺激的腹膜巨噬细胞的TNF α产生。我们的研究结果表明，GLP-1受体激动剂衰减血管损伤后的新生内膜形成。GLP-1受体激动剂或提高内源性GLP-1水平的药物可能有效治疗血管疾病。(C)2012爱思唯尔有限公司版权所有。
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.