2. Academic Validation
  3. Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis

Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis

  • Acta Pharmacol Sin. 2019 Oct;40(10):1314-1321. doi: 10.1038/s41401-019-0230-z.
Qiao Liao 1 2 3,  Shuang Qu 1 2 3,  Lu-Xun Tang 1 2 3,  Liang-Peng Li 1 2 3,  Duo-Fen He 1 2 3,  Chun-Yu Zeng 4 5 6,  Wei Eric Wang 7 8 9
Affiliations

Affiliations

  • 1 Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
  • 2 Chongqing Institute of Cardiology, Chongqing, 400042, China.
  • 3 Chongqing Cardiovascular Clinical Research Center, Chongqing, 400042, China.
  • 4 Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. chunyuzeng01@163.com.
  • 5 Chongqing Institute of Cardiology, Chongqing, 400042, China. chunyuzeng01@163.com.
  • 6 Chongqing Cardiovascular Clinical Research Center, Chongqing, 400042, China. chunyuzeng01@163.com.
  • 7 Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China. weiericwang@163.com.
  • 8 Chongqing Institute of Cardiology, Chongqing, 400042, China. weiericwang@163.com.
  • 9 Chongqing Cardiovascular Clinical Research Center, Chongqing, 400042, China. weiericwang@163.com.
PMID: 31061533 DOI: 10.1038/s41401-019-0230-z
Abstract

Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear. In this study we investigated the therapeutic effects of irisin in an acute MI model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for 2 weeks after MI. Cardiac function was assessed using echocardiography. We found that irisin administration significantly alleviated MI-induced cardiac dysfunction and ventricular dilation at 4 weeks post-MI. Irisin significantly reduced infarct size and fibrosis in post-MI hearts. Irisin administration significantly increased angiogenesis in the infarct border zone and decreased cardiomyocyte Apoptosis, but did not influence cardiomyocyte proliferation. In human umbilical vein endothelial cells (HUVEC), irisin significantly increased the phosphorylation of ERK, and promoted the migration of HUVEC detected in wound-healing and transwell chamber migration assay. The effects of irisin were blocked by the ERK Inhibitor U0126. In conclusion, irisin improves cardiac function and reduces infarct size in post-MI mouse heart. The therapeutic effect is associated with its pro-angiogenic function through activating ERK signaling pathway.

Keywords

ERK signal pathway; U0126; angiogenesis; irisin; myocardial infarction.

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