title: Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL cholesterol.
abstract: Evidence indicates that the high density lipoprotein (HDL) subfraction containing apolipoprotein A-I without apolipoprotein AII (LP-AI) is more antiatherogenic than HDL particles containing apolipoprotein A-I and apolipoprotein A-II (LP-AI+AII). This study examined the effect of extended-release niacin (niacin-ER) and gemfibrozil on LP-AI and LP-AI+AII particles in patients with low levels of HDL cholesterol (HDL-C). Mechanisms by which these agents modulate HDL particles were investigated by in vitro studies using human hepatoblastoma (Hep G2) cells. A total of 139 patients with low HDL-C (</=40 mg/dL) were randomized to niacin-ER or gemfibrozil in a multicenter double-blind trial. Patients were dose-escalated with once-nightly niacin-ER (1 to 2 g) or gemfibrozil (1.2 g) for 19 weeks. Niacin-ER had a greater effect in raising HDL-C and apolipoprotein A-I levels than did gemfibrozil. Niacin-ER at 1- and 2-g doses increased LP-AI levels by 8.7+/-4.0% (P=0.033) and 24.0+/-4.4% (P<0.001), respectively. Gemfibrozil had no consistent effect on LP-AI levels. LP-AI+AII levels increased 5% to 8% by both agents. In vitro studies showed that niacin, but not gemfibrozil, selectively decreased the uptake of (125)I-labeled LP-AI holoparticles by Hep G2 cells. The uptake of [(3)H]cholesterol ester was approximately 75% greater from LP-AI versus LP-AI+AII particles, but neither niacin nor gemfibrozil affected cholesterol ester uptake. These data indicate that unlike gemfibrozil, niacin selectively increases LP-AI compared with LP-AI+AII particle concentration in patients with low HDL-C levels. The mechanism of action of increased LP-AI concentration appears to be mediated by decreased hepatic removal of LP-AI particles, which are more efficient in reverse cholesterol transport, thus suggesting an additional mechanism by which niacin mediates its antiatherogenic properties.
authors.affiliation: Cholesterol Research Center, Department of Veterans Affairs Healthcare System, Long Beach, California, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sakai
authors.forename: V S
authors.initials: VS
authors.lastname: Kamanna
authors.forename: M L
authors.initials: ML
authors.lastname: Kashyap
mesh_terms: D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000097:blood; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015248:Gemfibrozil / Q000494:pharmacology*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000737:chemistry*; D009525:Niacin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D008055:Lipids; D008075:Lipoproteins, HDL; D009525:Niacin; D015248:Gemfibrozil