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. 中山大学附属第一医院高血压血管病科,广东 广州 510080
- 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:
[Objective]To investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/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.[Results]NMN 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 Ang Ⅱ-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).[Conclusion]NAD+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.
