Master of Science
Dr. Nica Borradaile
Niacin can reduce vascular disease risk, but its mechanism of action is controversial, and may not be dependent on systemic lipid modifying effects. This thesis tested the hypothesis that niacin directly improves endothelial cell function under lipotoxic and low oxygen conditions, as seen in ischemic conditions during metabolic syndrome, and investigated the potential mechanism involved. Human microvascular endothelial cell (HMVEC) survival was reduced by exposure to excess fatty acids under both normoxic and low oxygen conditions. Angiogenic function, as determined by tube formation on Matrigel, was impaired during fatty acid overload under either normoxic or low oxygen conditions. These effects were prevented by pretreatment with niacin, at a pharmacologically relevant dose, and appeared to be mediated by the niacin receptor, GPR109A, which we have recently shown to be expressed on human endothelial cells. In a mouse model of diet-induced obesity and metabolic syndrome, treatment with niacin improved functional recovery from acute ischemic injury. In conclusion, niacin improved HMVEC angiogenic function under lipotoxic and hypoxic conditions, effects that may translate to improved recovery from peripheral ischemia in vivo.
Pang, Dominic, "Niacin and microvascular endothelial cell response to fatty acid excess and hypoxia" (2014). Electronic Thesis and Dissertation Repository. 2294.