NAD+ Ameliorates Endothelial Dysfunction in Hypertension via Activation of SIRT3/IDH2 Signal Pathway
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20241122.001
- VernacularTitle:NAD+激活SIRT3/IDH2信号通路改善高血压血管内皮功能障碍
- Author:
Yumin QIU
1
;
Xi CHEN
1
;
Jianning ZHANG
1
;
Zhangchi LIU
1
;
Qiuxia ZHU
1
;
Meixin ZHANG
1
;
Jun TAO
1
;
Xing WU
1
Author Information
1. Department of Hypertension and Vascular Disease， The First Affiliated Hospital of Sun Yat-sen University， Guangzhou 510080，China
- Publication Type:Journal Article
- Keywords:
hypertension;
vascular endothelial injury;
nicotinamide adenine dinucleotide;
SIRT3;
oxidative stress
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(1):70-80
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD+. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD+ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.
