Meyers C Daniel, Liu Paul, Kamanna Vaijinath S, Kashyap Moti L
Long Beach Veterans Affairs Healthcare System, Long Beach, CA, United States.
Atherosclerosis. 2007 Jun;192(2):253-8. doi: 10.1016/j.atherosclerosis.2006.07.014. Epub 2006 Sep 1.
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 microM) 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 microM), 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.
烟酸是一种安全的广谱脂质药物，已被证明可预防心血管疾病，但其广泛应用受到前列腺素D2（PGD2）介导的烟酸潮红的限制。先前的研究表明，烟酸诱导的PGD2分泌是由皮肤介导的，但确切的细胞类型尚不清楚。我们假设巨噬细胞是烟酸诱导的PGD2分泌的来源，并进行了一系列实验来证实这一点。烟酸（0.1-3 mM）在培养的人巨噬细胞中诱导PGD2分泌，但在单核细胞或内皮细胞中则不然。PGD2分泌取决于烟酸的浓度和暴露时间。烟尿酸而非烟酰胺也诱导PGD2分泌。用阿司匹林（100 microM）对细胞进行预孵育可完全阻止烟酸对PGD2分泌的影响。烟酸的PGD2分泌作用与钙离子载体A23187（6 microM）的作用相加，但与细胞外钙无关。这些发现与最近的体内研究相结合，提供了证据表明巨噬细胞在介导烟酸潮红中起重要作用，并可能导致更好的策略来消除这种限制性副作用。
