Kuivenhoven J A, Groen A K
Department of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713GZ, Groningen, The Netherlands,
Handb Exp Pharmacol. 2015;224:285-300. doi: 10.1007/978-3-319-09665-0_8.
There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have identified a large number of factors that control HDL cholesterol levels. However, they have not resolved why HDL cholesterol and CVD are inversely related. A growing body of evidence from nongenetic studies shows that HDL in patients at increased risk of CVD has lost its protective properties and that increasing the cholesterol content of HDL does not result in the desired effects. Hopefully, these insights can help improve strategies to successfully intervene in HDL metabolism. It is clear that there is a need to revisit the HDL hypothesis in an unbiased manner. True insights into the molecular mechanisms that regulate plasma HDL cholesterol and triglycerides or control HDL function could provide the handholds that are needed to develop treatment for, e.g., type 2 diabetes and the metabolic syndrome. Especially genome-wide association studies have provided many candidate genes for such studies. In this review we have tried to cover the main molecular studies that have been produced over the past few years. It is clear that we are only at the very start of understanding how the newly identified factors may control HDL metabolism. In addition, the most recent findings underscore the intricate relations between HDL, triglyceride, and glucose metabolism indicating that these parameters need to be studied simultaneously.
有明确证据表明，血浆中高密度脂蛋白（HDL）胆固醇水平与心血管疾病（CVD）风险呈负相关。对患有遗传性HDL疾病的家族进行的研究以及一般（和患者）人群样本的基因关联研究已经确定了大量控制HDL胆固醇水平的因素。然而，它们尚未解决为什么HDL胆固醇与CVD呈负相关的问题。越来越多的非基因研究证据表明，CVD风险增加的患者体内的HDL已经失去了其保护特性，而且增加HDL的胆固醇含量并不会产生预期效果。有望这些见解能够帮助改进成功干预HDL代谢的策略。显然，有必要以无偏见的方式重新审视HDL假说。对调节血浆HDL胆固醇和甘油三酯或控制HDL功能的分子机制的真正见解，可能为开发针对例如2型糖尿病和代谢综合征的治疗方法提供所需的线索。尤其是全基因组关联研究为这类研究提供了许多候选基因。在这篇综述中，我们试图涵盖过去几年中进行的主要分子研究。显然，我们才刚刚开始理解新发现的因素如何控制HDL代谢。此外，最新研究结果强调了HDL、甘油三酯和葡萄糖代谢之间的复杂关系，表明这些参数需要同时进行研究。
