In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 116, No. suppl_16 ( 2007-10-16)
Abstract:
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 (O 2 .− ) 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 (5x10 5 cells) into nude mice using a carotid injury model. Furthermore, the effects of HDL on endothelial cell superoxide (O 2 . − ) 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 O 2 . − 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.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.116.suppl_16.II_16
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2007
detail.hit.zdb_id:
1466401-X
detail.hit.zdb_id:
80099-5
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