Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury

Wang, Lingqing1; Chen, Changgong1; Zhou, Hao2; Tao, Luyuan1; Xu, Enguo1

2024

10.7150/ijms.97530

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES   影响因子和分区

1449-1907

Myocardial ischemia-reperfusion (I/R) injury exacerbates cellular damage upon restoring blood flow to ischemic cardiac tissue, causing oxidative stress, inflammation, and apoptosis. This study investigates Nicotinamide Riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), for its cardioprotective effects. Administering NR to mice before I/R injury and evaluating heart function via echocardiography showed that NR significantly improved heart function, increased left ventricular ejection fraction (LVEF) and fractional shortening (FS), and reduced left ventricular end-diastolic (LVDd) and end-systolic diameters (LVSd). NR also restored E/A and E/e' ratios. It reduced cardiomyocyte apoptosis both in vivo and in vitro, inhibiting elevated caspase-3 activity and returning Bax protein levels to normal. In vitro, NR reduced the apoptotic rate in hydrogen peroxide (H2O2)-treated HL-1 cells from 30% to 10%. Mechanistically, NR modulated the SIRT3/mtROS/JNK pathway, reversing H2O2-induced SIRT3 downregulation, reducing mitochondrial reactive oxygen species (mtROS), and inhibiting JNK activation. Using SIRT3-knockout (SIRT3-KO) mice, we confirmed that NR's cardioprotective effects depend on SIRT3. Echocardiography showed that NR's benefits were abrogated in SIRT3-KO mice. In conclusion, NR provides significant cardioprotection against myocardial I/R injury by enhancing NAD+ levels and modulating the SIRT3/mtROS/JNK pathway, suggesting its potential as a novel therapeutic agent for ischemic heart diseases, meriting further clinical research.

Nicotinamide Riboside SIRT3 mtROS JNK cardiac ischemia reperfusion injury.

SCI

英语

其他

General & Internal Medicine

Medicine, General & Internal

WOS:001315501600012

IVYSPRING INT PUBL

Web of Science

1.Wenzhou Med Univ, Taizhou Peoples Hosp 1, Dept Cardiovasc Internal Med, Hengjie Rd 218, Taizhou, Zhejiang, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, Shenzhen, Guangdong, Peoples R China

Wang, Lingqing,Chen, Changgong,Zhou, Hao,et al. Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury[J]. INTERNATIONAL JOURNAL OF MEDICAL SCIENCES,2024,21(11).

Wang, Lingqing,Chen, Changgong,Zhou, Hao,Tao, Luyuan,&Xu, Enguo.(2024).Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury.INTERNATIONAL JOURNAL OF MEDICAL SCIENCES,21(11).

Wang, Lingqing,et al."Nicotinamide Riboside-Driven Modulation of SIRT3/mtROS/JNK Signaling Pathways Alleviates Myocardial Ischemia-Reperfusion Injury".INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 21.11(2024).