NAD(+) and Vascular Dysfunction: From Mechanisms to Therapeutic Opportunities

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.