Niacin increases human aortic endothelial Sirt1 activity and nitric oxide: effect on endothelial function and vascular aging

Objectives: Vascular endothelium, the innermost monolayer of endothelial cells lining the vessel wall, plays a vital physiologic role in the functional integrity of the aorta. Endothelialderived nitric oxide (NO) is an important molecule regulating vascular endothelial function by its vasodilatory properties and inhibiting pathological inflammatory and oxidative consequences of vascular aging and cardiovascular disorders. Sirtuin 1 (Sirt1), has recently emerged as an important regulator of vascular endothelial NO production. The effect of niacin on Sirt1 in human arterial tissue has not been studied. Methods: Using primary cultures of human aortic endothelial cells (HAEC), we examined the effect of niacin on endothelial Nicotinamide Adenine Dinucleotide+ (NAD+), Sirt1 and NO production. Results: In HAEC, we show that pharmacologically relevant doses of niacin at 0.2-0.3 mM for 24 h significantly increased cellular NAD+ levels, Sirt1 activity, and NO production as compared to controls. Using silencing of Sirt1 by siRNA, we observed that Sirt1 mediates niacin-induced NO production. Conclusions: Translationally, these findings suggest that Sirt1 activation by niacin may be one of the mechanisms of action of niacin acting on NO to improve endothelial function and mitigate human vascular aging and its deleterious cardiovascular consequences.