High-density lipoprotein-based drug discovery for treatment of atherosclerosis

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Abstract
Although there has been great progress achieved by the use of intensive statin therapy, the burden of atherosclerotic cardiovascular disease (CVD) remains high. This has initiated the search for novel high-density lipoprotein (HDL)-based therapeutics. Recent years have witnessed a shift from traditional raising HDL-C levels to enhancing HDL functionality, in which the process of reverse cholesterol transport (RCT) has acquired much attention. In this review, the authors describe the key factors involved in RCT process for potential drug targets to reduce the CVD risk. Furthermore, the review provides a summary of the effective screening methods that have been developed to target RCT and their applications. This review also introduces some new strategies currently being clinically developed, which have the potential to improve HDL function in the RCT process. It is rational that the functionality of HDL is more important than the plasma HDL-C level in the evaluation of pharmacological treatment in atherosclerosis. HDL-based strategies designed to promote macrophage RCT are a major area of current drug discovery and development for atherosclerotic diseases. A better understanding of the functionality of HDL and its relationship with atherosclerosis will expand our knowledge of the role of HDL in lipid metabolism, holding promise for a future successful HDL-based therapy.

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