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.