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01.09.2020 | Original Contribution

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

verfasst von: You-Jun Zhang, Mingchao Zhang, Xiaona Zhao, Kailei Shi, Maoqing Ye, Jiawen Tian, Shaofeng Guan, Weihai Ying, Xinkai Qu

Erschienen in: Basic Research in Cardiology | Ausgabe 5/2020

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Abstract

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.

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Titel: NAD+ administration decreases microvascular damage following cardiac ischemia/reperfusion by restoring autophagic flux
verfasst von: You-Jun Zhang
Mingchao Zhang
Xiaona Zhao
Kailei Shi
Maoqing Ye
Jiawen Tian
Shaofeng Guan
Weihai Ying
Xinkai Qu
Publikationsdatum: 01.09.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Basic Research in Cardiology / Ausgabe 5/2020
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-020-0817-z

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

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