Abstract
High Density Lipoproteins (HDLs) have long been considered as “good cholesterol,” beneficial to the whole body and, in particular, to cardio-vascular health. However, HDLs are complex particles that undergoes dynamic remodeling through interactions with various enzymes and tissues throughout their life cycle, making the complete understanding of its functions and roles more complicated than initially expected. In this review, we explore the novel understanding of HDLs' behavior in health and disease as a multifaceted class of lipoprotein, with different size subclasses, molecular composition, receptor interactions, and functionality. Further, we report on emergent HDL-based therapeutics tested in small and larger scale clinical trials and their mixed successes.
Highlights
Reviewed by: Oscar Perez-Mendez, Instituto Nacional de Cardiología, Mexico Emiel Van Der Vorst, Ludwig Maximilian University of Munich, Germany
The ILLUMINATE Phase 3 trial, using the drug torcetrapib, increased High Density Lipoproteins (HDL)-C content significantly through inhibition of cholesteryl ester transfer protein (CETPi), which normally catalyzes the transfer of cholesterol from HDL to low density lipoproteins (LDL), and triglycerides from LDL to HDL
Anacetrapib was the only CETPi to show modest reduction of major cardiovascular events over a follow-up period of 4 years in the REVEAL trial [7], the achieved benefits seem more attributable to the concomitant decrease in LDL-C, than to the HDL cholesterol (HDL-C) raising effects of the drug [9]
Summary
Reviewed by: Oscar Perez-Mendez, Instituto Nacional de Cardiología, Mexico Emiel Van Der Vorst, Ludwig Maximilian University of Munich, Germany. This review focuses on the relationship between structure and function as a multifaceted determinant of the complexity of HDLs. attention is paid to future perspectives about HDL as a potential vehicle for drug delivery and therapeutic agent against cardiovascular atherosclerotic disease.
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