Nicotinic acid induces secretion of prostaglandin D₂ in human macrophages: An in vitro model of the niacin flush

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• 作者：C. Daniel Meyers ; Paul Liu ; Vaijinath S. Kamanna ; Moti L. Kashyap
• 关键词：Nicotinic acid ; Niacin ; Flush ; Prostaglandin D₂ ; Dyslipidemia
• 刊名：Atherosclerosis
• 出版年：2007
• 出版时间：June 2007
• 年：2007
• 卷：192
• 期：2
• 页码：253-258
• 全文大小：278 K

文摘

Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D₂ (PGD₂) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD₂ secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD₂ secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1–3 mM) induced PGD₂ secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD₂ secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD₂ secretion. Pre-incubation of the cells with aspirin (100 μM) entirely prevented the nicotinic acid effects on PGD₂ secretion. The PGD₂ secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 μM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.