Effects of niacin in human vascular endothelial cells during lipotoxicity

Jennifer M. Hughes-Large, The University of Western Ontario

Abstract

Nicotinic acid (NA) can improve vascular function and regeneration independent of correcting dyslipidemia. NA, as a potential biosynthetic precursor for NAD⁺, may elicit these vascular benefits through SIRT-mediated NAD⁺-dependent responses. We hypothesized that NA improves endothelial cell function under lipotoxic conditions through NAD⁺-dependent pathways. Angiogenic function in excess palmitate was assessed by tube formation assay following treatment of human microvascular endothelial cells (HMVEC) with NA or nicotinamide mononucleotide (NMN; a direct NAD⁺ precursor). Both NA and NMN improved HMVEC angiogenic function during palmitate overload. Only NMN increased cellular NAD⁺ and SIRT1 activity, while both compounds activated SIRT2/3. By microarray, NA did not induce expression of known SIRT-regulated genes. However, we found that HMVEC robustly express NA receptor GRP109A, whose specific activation recapitulated NA-induced improvements in angiogenic function. We conclude that NA improves in vitro HMVEC angiogenic function under lipotoxic conditions, perhaps through GPR109A, but likely unrelated to NAD⁺ biosynthesis and SIRT activation.