Department of Internal Medicine, Medical University of Ioannina, Ioannina, Greece.
Laboratory of Clinical Chemistry, School of Medicine, University of Ioannina, Ioannina, Greece.
Curr Med Chem. 2020;27(18):2964-2978. doi: 10.2174/0929867326666190201142321.
As Mendelian Randomization (MR) studies showed no effect of variants altering HDL-cholesterol (HDL-C) levels concerning Cardiovascular Disease (CVD) and novel therapeutic interventions aiming to raise HDL-C resulted to futility, the usefulness of HDL-C is unclear.
As the role of HDL-C is currently doubtful, it is suggested that the atheroprotective functions of HDLs can be attributed to the number of HDL particles, and their characteristics including their lipid and protein components. Scientific interest has focused on HDL function and on the causes of rendering HDL particles dysfunctional, whereas the relevance of HDL subclasses with CVD remains controversial.
The present review discusses changes in quality as much as in quantity of HDL in pathological conditions and the connection between HDL particle concentration and cardiovascular disease and mortality. Emphasis is given to the recently available data concerning the cholesterol efflux capacity and the parameters that determine HDL functionality, as well as to recent investigations concerning the associations of HDL subclasses with cardiovascular mortality.
MR studies or pharmacological interventions targeting HDL-C are not in favor of the hypothesis of HDL-C levels and the relationship with CVD. The search of biomarkers that relate with HDL functionality is needed. Similarly, HDL particle size and number exhibit controversial data in the context of CVD and further studies are needed.
There is no room for the old concept of HDL as a silver bullet,as HDL-C cannot be considered a robust marker and does not reflect the importance of HDL particle size and number. Elucidation of the complex HDL system, as well as the finding of biomarkers, will allow the development of any HDL-targeted therapy.
孟德尔随机化 (MR) 研究表明，改变高密度脂蛋白胆固醇 (HDL-C) 水平的变异体对心血管疾病 (CVD) 没有影响，而旨在提高 HDL-C 的新治疗干预措施也无果而终，因此 HDL-C 的作用尚不清楚。
由于 HDL-C 的作用目前存在疑问，因此有人认为 HDL 的抗动脉粥样硬化功能可以归因于 HDL 颗粒的数量及其特征，包括其脂质和蛋白质成分。科学研究的重点是 HDL 的功能以及导致 HDL 颗粒功能失调的原因，而 HDL 亚类与 CVD 的相关性仍存在争议。
本综述讨论了在病理条件下 HDL 的质量和数量的变化，以及 HDL 颗粒浓度与心血管疾病和死亡率之间的关系。重点介绍了最近关于胆固醇流出能力和决定 HDL 功能的参数的可用数据，以及最近关于 HDL 亚类与心血管死亡率之间关联的研究。
针对 HDL-C 的 MR 研究或药物干预并不支持 HDL-C 水平与 CVD 之间的假设。需要寻找与 HDL 功能相关的生物标志物。同样，在 CVD 背景下，HDL 颗粒大小和数量的数据存在争议，需要进一步研究。
HDL 作为万能药的旧概念已不再适用，因为 HDL-C 不能被视为一个可靠的标志物，也不能反映 HDL 颗粒大小和数量的重要性。阐明复杂的 HDL 系统以及寻找生物标志物将有助于开发任何针对 HDL 的治疗方法。
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