Effects of Niacin and Vitamin D on Endothelial Cell Angiogenic Function and Vascular Regeneration During Lipotoxicity
Abstract
Observational studies have suggested an association between low levels of niacin and vitamin D and increased cardiovascular disease risk. Both vitamins have been shown to improve endothelial functions and vascular regeneration following vascular injury, however, it appears vitamin D may promote or inhibit neovascularization in a context-dependent manner. We hypothesized that supplementation of vitamin D alone and in combination with niacin, would improve endothelial cell function under lipotoxic conditions and promote revascularization and functional recovery in obese mice with ischemic injury. Matrigel assays, mRNA microarray analyses and growth rate assays were used to investigate angiogenic function of endothelial cells exposed to the saturated fatty acid, palmitate. Supplementation with vitamin D, niacin, and the combination improved endothelial tube formation and stability in high palmitate. Supplementation with vitamin D markedly decreased expression of cell cycle regulators, where niacin induced stable expression of miR126, a known regulator of angiogenesis. In diet-induced obese mice with acute ischemic injury, treatment with niacin, but not vitamin D or the combination, improved hind limb functional recovery. No significant improvements in revascularization, regeneration, inflammation, or fibrosis were observed. In conclusion, although both vitamins promoted in vitro endothelial cell angiogenic function, only niacin improved functional recovery following ischemic injury.