NAD+ administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux

• DOI: 10.1007/s00395-020-0817-z
• Publication Date: 2020-08-10T21:02:54Z
• Authors: You-Jun Zhang; Mingchao Zhang; Xiaona Zhao; Kailei Shi; Maoqing Ye; Jiawen Tian; Shaofeng Guan; Weihai Ying; Xinkai Qu
• Keywords: Male; 0301 basic medicine; Drug Evaluation, Preclinical; Myocardial Reperfusion Injury; Cell Separation; NAD; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Microvessels; Autophagy; Animals; Endothelium, Vascular

Microvascular damage is a key pathological change in myocardial ischemia/reperfusion (I/R) injury. Using a rat model of myocardial I/R, our current study has provided the first evidence that nicotinamide adenine dinucleotide (NAD+) administration can significantly attenuate myocardial I/R-induced microvascular damage, including reduced regional blood perfusion, decreased microvessel density and integrity, and coronary microvascular endothelial cells (CMECs) injury. In studies with primary cultured CMECs under hypoxia/reoxygenation (HR) and a rat model of I/R, our results suggested that the protective effect of NAD+ on CMECs exposed to HR or I/R is at least partially mediated by the NAD+-induced restoration of autophagic flux, especially lysosomal autophagy: NAD+ treatment markedly induced transcription factor EB (TFEB) activation and attenuated lysosomal dysfunction in the I/R or HR-exposed cells. Collectively, our study has provided the first in vivo and in vitro evidence that NAD+ significantly rescued the impaired autophagic flux and cell apoptosis that was induced by I/R in rat CMECs, which is mediated in part through the action of TFEB-mediated lysosomal autophagy.