Abstract 189: Extended-Release Niacin Improves Endothelial Function, Restores Re-Endothelialization Capacity of Endothelial Progenitor Cells and Augments Vasoprotective Properties of HDL in Patients with Metabolic Syndrome
Background: High density lipoprotein (HDL)-targeted therapies are currently evaluated as a novel therapeutic strategy for cardiovascular disease. However, recent data suggest that HDL may become dysfunctional in metabolic syndrome (MetS). We therefore evaluated the effect of extended-release niacin (ERN) on endothelial function, re-endothelialization capacity of endothelial progenitor cells (EPC) and HDL quality, i.e. the capacity of HDL to stimulate endothelial nitric oxide (NO) production and reduce superoxide (O2.−) production.
Methods and Results: Thirty MetS patients were randomized to 3 month treatment with ERN (1500 mg/d) or placebo. Flow-dependent, endothelium-mediated vasodilation (FDD) was characterized by high-resolution ultrasound, EPCs were cultured and HDL was isolated by ultracentrifugation before and after therapy. In vivo re-endothelialization capacity of EPCs was tested by transplantation of EPCs (5x105 cells) into nude mice using a carotid injury model. Furthermore, the effects of HDL on endothelial cell superoxide (O2. −) and NO production were determined by electron spin resonance spectroscopy. ERN therapy significantly raised HDL levels (36.4±4.2 vs. 43.4±6.9 mg/dl, P <0.01), whereas no change was observed after placebo (35.9±6.2 vs. 33.7±6.1 mg/dl, P n.s.). FDD was improved by ERN (5.2±1.8 vs 9.8±2.2%; P<0.01), but not after placebo therapy (4.9±1.5 vs. 4.3±0.9 %; P n.s.). Moreover, the re-endothelialization capacity of EPCs was markedly increased after ERN, but not after placebo (REA-ERN: 34±9%; P<0.001 vs. placebo). Importantly, HDL isolated after ERN, but not after placebo therapy stimulated endothelial cell NO production and inhibited endothelial cell O2. − production, suggesting that improved vasoprotective properties of HDL contributed to beneficial effects of ERN therapy on endothelial function.
Conclusions: The present study demonstrates that extended-release niacin improves endothelium-dependent vasodilation, restores re-endothelialization capacity of EPCs and importantly improves vasoprotective functions of HDL from patients with metabolic syndrome. These data suggest that extended-release niacin therapy has a beneficial effect on HDL vasoprotective qualities.