Montecucco Fabrizio, Quercioli Alessandra, Dallegri Franco, Viviani Giorgio Luciano, Mach François
Cardiology Division, Department of Medicine, Geneva University Hospital, Foundation for Medical Research, 64 Avenue Roseraie, Geneva, Switzerland.
Expert Rev Cardiovasc Ther. 2010 Oct;8(10):1457-67. doi: 10.1586/erc.10.116.
Nicotinic acid (at a daily dose of grams) has been shown to induce potent anti-atherosclerotic effects in human and animal models. Evidence from clinical studies performed in the 1950s has shown that nicotinic acid treatment remarkably improves the plasma lipid profile. Large clinical studies showed that nicotinic acid improves clinical cardiovascular outcomes. Given the protective effects of niacin, basic research studies were designed to explore additional anti-atherosclerotic pathways, such as those involved in cardiovascular inflammation. After the discovery of the nicotinic acid receptor GPR109A on adipocytes and immune cells, novel direct immunomodulatory properties of nicotinic acid have been identified. Importantly, the regulation of the release of inflammatory mediators from adipose tissue was observed, independent of lipid level amelioration. Less is known about the possible direct anti-inflammatory activities of nicotinic acid in other cells (such as hepatocytes, endothelial and vascular cells) previously indicated as key players in atherogenesis. Thus, further studies are needed to clarify this promising topic. Emerging evidence from clinical and basic research studies indicates that novel direct anti-atherosclerotic properties might mediate nicotinic acid-induced cardiovascular protection. Despite some limitations in its clinical use (mainly due to the incidence of adverse events, such as cutaneous flushing and hepatotoxicity), nicotinic acid should be considered as a very potent therapeutic approach to reduce atherosclerosis. Promising research developments are warranted in the near future.
烟酸（每日剂量达数克）已被证明在人类和动物模型中具有强大的抗动脉粥样硬化作用。20世纪50年代进行的临床研究证据表明，烟酸治疗可显著改善血浆脂质谱。大型临床研究表明，烟酸可改善临床心血管结局。鉴于烟酸的保护作用，开展了基础研究以探索其他抗动脉粥样硬化途径，如参与心血管炎症的途径。在脂肪细胞和免疫细胞上发现烟酸受体GPR109A后，已确定了烟酸新的直接免疫调节特性。重要的是，观察到烟酸对脂肪组织炎症介质释放的调节作用，且与脂质水平改善无关。对于烟酸在先前被认为是动脉粥样硬化关键参与者的其他细胞（如肝细胞、内皮细胞和血管细胞）中可能的直接抗炎活性，人们了解较少。因此，需要进一步研究来阐明这一有前景的课题。临床和基础研究的新证据表明，新的直接抗动脉粥样硬化特性可能介导了烟酸诱导的心血管保护作用。尽管其临床应用存在一些局限性（主要是由于不良事件的发生率，如皮肤潮红和肝毒性），但烟酸仍应被视为一种非常有效的降低动脉粥样硬化的治疗方法。在不久的将来，有望取得有前景的研究进展。
