J Lipid Atheroscler.  2022 May;11(2):111-132. 10.12997/jla.2022.11.2.111.

NAD ⁺ and Vascular Dysfunction: From Mechanisms to Therapeutic Opportunities

• Abdellatif M
• Bugger H
• Kroemer G
• Sedej S

• KMID: 2531861
• DOI: http://doi.org/10.12997/jla.2022.11.2.111

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.

Keyword

Vascular disease; Hypertension; Nicotinamide adenine dinucleotide; Inflammation; Mitochondria; Autophagy; Aging