Mitochondrial Aldehyde Dehydrogenase 2 Regulates Revascularization in Chronic Ischemia: Potential Impact on the Development of Coronary Collateral Circulation

Arteriosclerosis, Thrombosis, and Vascular Biology
Xiangwei LiuAijun Sun

Abstract

Revascularization is an essential process to compensate for cardiac underperfusion and, therefore, preserves cardiac function in the face of chronic ischemic injury. Recent evidence suggested a vital role of aldehyde dehydrogenase 2 (ALDH2) in cardiac protection after ischemia. This study was designed to determine whether ALDH2 regulates chronic ischemia-induced angiogenesis and to explore the underlying mechanism involved. Moreover, the clinical impact of the ALDH2 mutant allele on the development of coronary collateral circulation (CCC) was evaluated. Mice limb ischemia was performed. Compared with wild-type, ALDH2 deletion significantly reduced perfusion recovery, small artery and capillary density, and increased muscle atrophy in this ischemic model. In vitro, ALDH2-knockdown reduced proliferation, migration and hypoxia triggered endothelial tube formation of endothelial cells, the effects of which were restored by ALDH2 transfection. Further examination revealed that ALDH2 regulated angiogenesis possibly through hypoxia-inducible factor-1α/vascular endothelial growth factor pathways. To further discern the role of ALDH2 deficiency in the function of bone marrow stem/progenitor cells, cross bone marrow transplantation was p...Continue Reading

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Citations

Apr 29, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Yao XieQingbo Xu
Feb 13, 2018·Expert Opinion on Therapeutic Targets·Thomas Münzel, Andreas Daiber
Mar 30, 2017·Frontiers in Physiology·Victoria G RontoyanniCraig Porter
Jan 11, 2019·Chemical Research in Toxicology·José Salud Rodríguez-ZavalaBelem Yoval-Sánchez

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