Aging, Smooth Muscle Vitality, and Aortic Integrity

Abstract

Advances in medical genetics and imaging have resulted in a significant increase in the number of diagnosed thoracic aortic aneurysms. Recent findings establish a link between diminished nicotinamide phosphoribosyltransferase (NAMPT) and compromised smooth muscle cell vitality in aortic dilatation. These findings have myriad implications given the diverse roles of NAMPT, which is central to the production of nicotinamide adenine dinucleotide (NAD⁺), and thus ATP production, as well the activity of multiple NAD⁺ consuming proteins. Given its central role in vascular cell vitality and thus matrix integrity, further attention should be directed to the NAMPT-NAD⁺ control system in thoracic aortopathy.

Keywords: ATP; Editorials; actomyosin activity; apoptosis; inflammation; mechanotransduction.

Figure 1

Healthy (spindle-shaped; left) and unhealthy (rounded; right) vascular SMCs, the latter with few connections to ECM and lower actomyosin activity. Shown too, the salvage biosynthesis pathway with select NAD⁺ consuming proteins (SIRT1, PARP1) leading to important biological outcomes. Increased NAMPT-NAD⁺ has multiple effects, including suppression of inflammation and direct and indirect influences on contractility. NMNAT = nicotinamide mononucleotide adenylyltransferase 1, NADH = nicotinamide adenine dinucleotide hydrate, ROS = reactive oxygen species, and pMLC (phosphorylated myosin light chain). Courtesy Dr. S-I. Murtada.