Niacin has modest but overall favorable effects on plasma lipids by increasing high density lipoprotein cholesterol (HDL-C) and lowering triglycerides. Clinical trials, however, evaluating niacin therapy for prevention of cardiovascular outcomes have returned mixed results. Recent evidence suggests that the HDL proteome may be a better indicator of HDL’s cardioprotective function than HDL-C. The objective of this study was to evaluate the effect of niacin monotherapy on HDL protein composition and function. A 20-week investigational study was performed with 11 participants receiving extended-release niacin (target dose = 2 g/day) for 16-weeks followed by a 4-week washout period. HDL was isolated from participants at weeks: 0, 16, and 20. The HDL proteome was analyzed at each time point by mass spectrometry and relative protein quantification was performed by label-free precursor ion intensity measurement. In this cohort, niacin therapy had typical effects on routine clinical lipids (HDL-C + 16%, q < 0.01; LDL-C − 20%, q < 0.01; and triglyceride − 15%, q = 0.1). HDL proteomics revealed significant effects of niacin on 5 proteins: serum amyloid A (SAA), angiotensinogen (AGT), apolipoprotein A-II (APOA2), clusterin (CLUS), and apolipoprotein L1 (APOL1). SAA was the most prominently affected protein, increasing 3-fold in response to niacin (q = 0.008). Cholesterol efflux capacity was not significantly affected by niacin compared to baseline, however, stopping niacin resulted in a 9% increase in efflux (q < 0.05). Niacin did not impact HDL’s ability to influence endothelial function. Extended-release niacin therapy, in the absence of other lipid-modifying medications, can increase HDL-associated SAA, an acute phase protein associated with HDL dysfunction.

中文翻译：

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烟酸单一疗法对高密度脂蛋白组成和功能的影响。

烟酸通过增加高密度脂蛋白胆固醇 (HDL-C) 和降低甘油三酯对血脂有适度但总体有利的影响。然而，评估烟酸治疗预防心血管结果的临床试验结果喜忧参半。最近的证据表明，与 HDL-C 相比，HDL 蛋白质组可能是 HDL 心脏保护功能的更好指标。本研究的目的是评估烟酸单一疗法对 HDL 蛋白质组成和功能的影响。进行了一项为期 20 周的研究，11 名参与者接受了 16 周的缓释烟酸（目标剂量 = 2 克/天），然后是 4 周的清除期。在第 0、16 和 20 周从参与者中分离出 HDL。通过质谱法在每个时间点分析 HDL 蛋白质组，并通过无标记前体离子强度测量进行相对蛋白质定量。在该队列中，烟酸治疗对常规临床血脂有典型影响（HDL-C + 16%，q < 0.01；LDL-C − 20%，q < 0.01；和甘油三酯 − 15%，q = 0.1）。HDL 蛋白质组学揭示了烟酸对 5 种蛋白质的显着影响：血清淀粉样蛋白 A (SAA)、血管紧张素原 (AGT)、载脂蛋白 A-II (APOA2)、凝聚素 (CLUS) 和载脂蛋白 L1 (APOL1)。SAA 是受影响最显着的蛋白质，对烟酸的反应增加了 3 倍（q = 0.008）。与基线相比，烟酸对胆固醇外排能力没有显着影响，然而，停止烟酸导致外排增加 9% (q < 0.05)。烟酸不影响 HDL 影响内皮功能的能力。在没有其他调脂药物的情况下，缓释烟酸疗法可以增加与 HDL 相关的 SAA，这是一种与 HDL 功能障碍相关的急性期蛋白。