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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:115

Enthalten in:

Basic research in cardiology - 115(2020), 5 vom: 10. Aug., Seite 57

Sprache:

Englisch

Beteiligte Personen:

Zhang, You-Jun [VerfasserIn]
Zhang, Mingchao [VerfasserIn]
Zhao, Xiaona [VerfasserIn]
Shi, Kailei [VerfasserIn]
Ye, Maoqing [VerfasserIn]
Tian, Jiawen [VerfasserIn]
Guan, Shaofeng [VerfasserIn]
Ying, Weihai [VerfasserIn]
Qu, Xinkai [VerfasserIn]

Links:

Volltext

Themen:

0U46U6E8UK
Autophagic flux
Journal Article
Lysosomes
Microvascular damage
Myocardial ischemia
NAD
NAD+
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 25.06.2021

Date Revised 25.06.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s00395-020-0817-z

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313538344