MicroRNA-133a impairs perfusion recovery after hindlimb ischemia in diabetic mice

Bioscience Reports - Tập 38 Số 4 - 2018
Lingdan Chen1, Бо Лю1, Dejun Sun2, Tao Wang1, Li Zhao1, Wenli Chen1, Mingjie Yuan3, Jian Wang1, Wenju Lu1
1State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
2Department of Respiratory Medicine, Inner Mongolia Autonomous Region People's Hospital, Hohhot 010017, Inner Mongolia Autonomous Region, China
3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430071, China

Tóm tắt

Objective: Peripheral arterial disease (PAD) patients with diabetes mellitus suffer from impaired neovascularization after ischemia which results in poorer outcomes. MicroRNA (miR)-133a is excessively expressed in endothelial cells under diabetic conditions. Here, we test whether diabetes-induced miR-133a up-regulation is involved in the impaired capability of neovascularization in experimental PAD models. Methods and results: MiR-133a level was measured by quantitative RT-PCR and showed a higher expression level in the ischemic muscle from diabetic mice when compared with nondiabetic mice. Knockdown of miR-133a using antagomir improved perfusion recovery and angiogenesis in experimental PAD model with diabetes day 21 after HLI. On the other hand, overexpression of miR-133a impaired perfusion recovery. Ischemic muscle was harvested day 7 after experimental PAD for biochemical test, miR-133a antagonism resulted in reduced malondialdehyde, and it increased GTP cyclohydrolase 1 (GCH1), and cyclic guanine monophosphate (cGMP) levels. In cultured endothelial cells, miR-133a antagonism resulted in reduced reactive oxygen species level, and it increased tube formation, nitric oxide (NO), and cGMP level. Moreover, miR-133a antagonism-induced angiogenesis was abolished by GCH1 inhibitor. In contrary, miR-133a overexpression impairs angiogenesis and it reduces GCH1, NO, and cGMP levels in nondiabetic models. Conclusion: Diabetes mellitus-induced miR-133a up-regulation impairs angiogenesis in PAD by reducing NO synthesis in endothelial cells. MiR-133a antagonism improves postischemic angiogenesis.

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Tập 38 Số 4

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