Deletion of AT2 Receptor Prevents SHP-1-Induced VEGF Inhibition and Improves Blood Flow Reperfusion in Diabetic Ischemic Hindlimb
Deletion of AT2 Receptor Prevents SHP-1-Induced VEGF Inhibition and Improves Blood Flow Reperfusion in Diabetic Ischemic Hindlimb
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DOI：
10.1161/atvbaha.117.309977
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发表时间：
2017-01-01
影响因子：
8.7
通讯作者：
Geraldes, Pedro
中科院分区：
文献类型：
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作者：
Paquin-Veillette, Judith;Lizotte, Farah;Geraldes, Pedro
目的-股动脉狭窄引起的缺血是影响糖尿病患者的外周动脉疾病和发病率的主要原因。我们之前曾报道，糖尿病小鼠中 VEGF（血管内皮生长因子）血管生成反应的抑制与 SHP-1（含 SH2 结构域的磷酸酶 1）表达增加有关，SHP-1 是一种可以被 AT2（血管紧张素 II 2 型）受体激活的蛋白质。 AT2 受体的缺失已被证明可以促进缺血肌肉内的血管生成。然而，AT2受体在糖尿病状况中的相对影响仍不清楚。方法和结果-非糖尿病和糖尿病AT2缺失(Atgr2(-/Y))小鼠在糖尿病2个月后接受股动脉结扎。每周测量血液灌注
Objective-Ischemia caused by narrowing of femoral artery is a major cause of peripheral arterial disease and morbidity affecting patients with diabetes mellitus. We have previously reported that the inhibition of the angiogenic response to VEGF (vascular endothelial growth factor) in diabetic mice was associated with the increased expression of SHP-1 (SH2 domain-containing phosphatase 1), a protein that can be activated by the AT2 (angiotensin II type 2) receptor. Deletion of AT2 receptor has been shown to promote angiogenesis within the ischemic muscle. However, the relative impact of AT2 receptor in diabetic condition remains unknown.Approach and Results-Nondiabetic and diabetic AT2 null (Atgr2(-/Y)) mice underwent femoral artery ligation after 2 months of diabetes mellitus. Blood perfusion was measured every week