Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria.
Agaplesion Markus Krankenhaus, 60431 Frankfurt, Germany.
Biomolecules. 2020 Sep 21;10(9):1348. doi: 10.3390/biom10091348.
In the general population, the ability of high-density lipoproteins (HDLs) to promote cholesterol efflux is a predictor of cardiovascular events, independently of HDL cholesterol levels. Although patients with chronic kidney disease (CKD) have a high burden of cardiovascular morbidity and mortality, neither serum levels of HDL cholesterol, nor cholesterol efflux capacity associate with cardiovascular events. Important for the following discussion on the role of HDL in CKD is the notion that traditional atherosclerotic cardiovascular risk factors only partially account for this increased incidence of cardiovascular disease in CKD. As a potential explanation, across the spectrum of cardiovascular disease, the relative contribution of atherosclerotic cardiovascular disease becomes less important with advanced CKD. Impaired renal function directly affects the metabolism, composition and functionality of HDL particles. HDLs themselves are a heterogeneous population of particles with distinct sizes and protein composition, all of them affecting the functionality of HDL. Therefore, a more specific approach investigating the functional and compositional features of HDL subclasses might be a valuable strategy to decipher the potential link between HDL, cardiovascular disease and CKD. This review summarizes the current understanding of the relationship of HDL composition, metabolism and function to their cardio-protective properties in CKD, with a focus on CKD-induced changes in the HDL proteome and reverse cholesterol transport capacity. We also will highlight the gaps in the current knowledge regarding important aspects of HDL biology.
在普通人群中，高密度脂蛋白（HDL）促进胆固醇外排的能力是心血管事件的预测因子，独立于 HDL 胆固醇水平。尽管慢性肾脏病（CKD）患者的心血管发病率和死亡率负担很高，但 HDL 胆固醇的血清水平，以及胆固醇外排能力均与心血管事件无关。以下关于 HDL 在 CKD 中的作用的讨论中，重要的是这样一种观点，即传统的动脉粥样硬化心血管危险因素仅部分解释了 CKD 中这种心血管疾病发病率的增加。作为一种潜在的解释，在心血管疾病的整个范围内，随着 CKD 的进展，动脉粥样硬化心血管疾病的相对贡献变得不那么重要。肾功能受损直接影响 HDL 颗粒的代谢、组成和功能。HDL 本身是一种具有不同大小和蛋白组成的异质颗粒群体，所有这些都影响 HDL 的功能。因此，更具体地研究 HDL 亚类的功能和组成特征可能是一种有价值的策略，可以揭示 HDL、心血管疾病和 CKD 之间的潜在联系。这篇综述总结了目前对 HDL 组成、代谢和功能与它们在 CKD 中的心脏保护特性之间关系的理解，重点是 CKD 引起的 HDL 蛋白质组和胆固醇逆向转运能力的变化。我们还将突出当前关于 HDL 生物学重要方面的知识空白。
