NAD⁺ and Vascular Dysfunction: From Mechanisms to Therapeutic Opportunities

Abstract

Nicotinamide adenine dinucleotide (NAD + ) is an essential and pleiotropic coenzyme involved not only in cellular energy metabolism, but also in cell signaling, epigenetic regulation, and post-translational protein modifications. Vascular disease risk factors are associated with aberrant NAD + metabolism. Conversely, the therapeutic increase of NAD + levels through the administration of NAD + precursors or inhibitors of NAD + -consuming enzymes reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular pathologies. As such, NAD + has emerged as a potential target for combatting age-related cardiovascular and cerebrovascular disorders. This review discusses NAD + -regulated mechanisms critical for vascular health and summarizes new advances in NAD + research directly related to vascular aging and disease, including hypertension, atherosclerosis, coronary artery disease, and aortic aneurysms. Finally, we enumerate challenges and opportunities for NAD + repletion therapy while anticipating the future of this exciting research field, which will have a major impact on vascular medicine.

Plant-Based Diet and Supplements Reduced COVID-19 Severity and Mortality in Elderly Patients with Multiple Comorbidities (Part 2: Exploring the Underlying Mechanisms of Successful Intervention)

“…NAD + has been shown to reduce chronic inflammation, reactivate autophagy, and assist mitochondrial biogenesis. These findings suggest that supplementing with precursor NAD+ may be a useful therapeutic approach for treating these conditions [97], as we have done for our elderly patients long before the pandemic. Further research is required before recommending the use of precursor NAD+ to reduce the severity and mortality of COVID-19 patients.…”

Intestinal microbiota and metabolome perturbations in ischemic and idiopathic dilated cardiomyopathy

“…Previous studies have reported that ischemia in cardiomyocytes resulted in NAD + depletion, reduced available ATP, and mitochondrial dysfunction [ 65 ]. Supplementation of nicotinic acid restored NAD + balance, improved abnormal blood flow conditions and alleviated ischemia–reperfusion injury [ 66 ]. Similarly, NAD + levels showed a significant decrease in different types of DCM [ 67 , 68 ].…”

Intermedin Alleviates Vascular Calcification in CKD through Sirtuin 3-Mediated Inhibition of Mitochondrial Oxidative Stress

“…Sirt3 is a NAD + -dependent deacetylase predominantly located in mitochondria [ 32 ]. Enzymatic activity of Sirt3 is reduced by mitochondrial dysfunction due to repressed mitochondrial NAD + levels, leading to dysregulation of mechanisms for mitochondrial homeostasis maintenance [ 33 , 34 ]. Meanwhile, impaired mitochondrial function affects the utilization of acetyl-CoA in mitochondria, leading to the accumulation of acetyl-CoA in mitochondria, which impairs the function of mitochondrial proteins, such as SOD2 [ 35 ], through nonenzymatic acetylation modification [ 36 ].…”