Digby Janet E, Lee Justin M S, Choudhury Robin P
Department of Cardiovascular Medicine, University of Oxford, Oxford, UK.
Curr Opin Lipidol. 2009 Aug;20(4):321-6. doi: 10.1097/MOL.0b013e32832d3b9d.
Nicotinic acid is the most potent treatment clinically available for lowering LDL cholesterol and VLDL cholesterol and raising HDL cholesterol. The strong inverse relationship between coronary heart disease risk and HDL cholesterol at all levels of LDL cholesterol has, therefore, given renewed emphasis on the therapeutic potential of niacin. The purpose of this review is to evaluate advances in the elucidation of mechanisms by which nicotinic acid affects the lipoprotein profile and, more recently, emerging evidence of nonlipid-mediated anti-inflammatory effects.
Niacin treatment reduces cardiovascular events and the progression of atherosclerosis. Identification of G-protein-coupled receptor 109A as the receptor for nicotinic acid has provided insights into how treatment with this compound leads to a favourable alteration in HDL cholesterol. In addition, evidence of nonlipid-mediated anti-inflammatory effects of nicotinic acid such as direct enhancement of adiponectin secretion demonstrates a novel atheroprotective role.
Whether nicotinic acid use becomes routine in the treatment of atherosclerosis is likely to be determined by the results of two ongoing clinical outcome trials. In addition, further research is required to explore the 'pleiotropic' effects of nicotinic acid and will ultimately provide a platform for the development of newer molecules that are potentially beneficial but without the well known side-effects.
烟酸是临床上可用于降低低密度脂蛋白胆固醇(LDL-C)和极低密度脂蛋白胆固醇(VLDL-C)以及升高高密度脂蛋白胆固醇(HDL-C)的最有效治疗药物。因此,在所有LDL-C水平下,冠心病风险与HDL-C之间的强烈负相关关系重新强调了烟酸的治疗潜力。本综述的目的是评估在阐明烟酸影响脂蛋白谱的机制方面取得的进展,以及最近出现的非脂质介导的抗炎作用的证据。
烟酸治疗可减少心血管事件和动脉粥样硬化的进展。将G蛋白偶联受体109A鉴定为烟酸的受体,为了解该化合物的治疗如何导致HDL-C的有利改变提供了线索。此外,烟酸的非脂质介导的抗炎作用的证据,如直接增强脂联素分泌,证明了一种新的抗动脉粥样硬化作用。
烟酸是否会成为动脉粥样硬化治疗的常规用药,可能取决于两项正在进行的临床结局试验的结果。此外,还需要进一步研究来探索烟酸的“多效性”作用,并最终为开发可能有益但没有众所周知副作用的新型分子提供一个平台。