Savolainen Markku J
Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, Kajaanintie 50, 5000, 90014, Oulu, Finland,
Handb Exp Pharmacol. 2015;224:259-83. doi: 10.1007/978-3-319-09665-0_7.
Epidemiological studies have shown an inverse association between high-density lipoprotein cholesterol (HDL-C) levels and risk of ischemic heart disease. In addition, a low level of HDL-C has been shown to be a risk factor for other diseases not related to atherosclerosis. However, recent studies have not supported a causal effect of HDL-C in the development of atherosclerosis. Furthermore, new drugs markedly elevating HDL-C levels have been disappointing with respect to clinical endpoints. Earlier, most studies have focused almost exclusively on the total HDL-C without regard to the chemical composition or multiple subclasses of HDL particles. Recently, there have been efforts to dissect the HDL fraction into as many well-defined subfractions and individual molecules of HDL particles as possible. On the other hand, the focus is shifting from the structure and composition to the function of HDL particles. Biomarkers and mechanisms that could potentially explain the beneficial characteristics of HDL particles unrelated to their cholesterol content have been sought with sophisticated methods such as proteomics, lipidomics, metabonomics, and function studies including efflux capacity. These new approaches have been used in order to resolve the complex effects of diseases, conditions, environmental factors, and genes in relation to the protective role of HDL but high-throughput methods are still needed for large-scale epidemiological studies.
流行病学研究表明，高密度脂蛋白胆固醇（HDL-C）水平与缺血性心脏病风险呈负相关。此外，低水平的HDL-C已被证明是其他与动脉粥样硬化无关疾病的危险因素。然而，最近的研究并不支持HDL-C在动脉粥样硬化发展中的因果作用。此外，显著提高HDL-C水平的新药在临床终点方面令人失望。早期，大多数研究几乎只关注总HDL-C，而不考虑HDL颗粒的化学组成或多个亚类。最近，人们努力将HDL组分尽可能分解为定义明确的亚组分和HDL颗粒的单个分子。另一方面，重点正从HDL颗粒的结构和组成转向其功能。人们已经通过蛋白质组学、脂质组学、代谢组学等复杂方法以及包括流出能力在内的功能研究，寻找可能解释HDL颗粒与其胆固醇含量无关的有益特性的生物标志物和机制。这些新方法已被用于解析疾病、状况、环境因素和基因与HDL保护作用相关的复杂影响，但大规模流行病学研究仍需要高通量方法。
