Abstract
High Density Lipoprotein (HDL) particles, beyond serving as lipid transporters and playing a key role in reverse cholesterol transport, carry a highly variable number of proteins, micro-RNAs, vitamins, and hormones, which endow them with the ability to mediate a plethora of cellular and molecular mechanisms that promote cardiovascular health. It is becoming increasingly evident, however, that the presence of cardiovascular risk factors and co-morbidities alters HDLs cargo and protective functions. This concept has led to the notion that metrics other than HDL-cholesterol levels, such as HDL functionality and composition, may better capture HDL cardiovascular protection. On the other hand, the potential of HDL as natural delivery carriers has also fostered the design of engineered HDL-mimetics aiming to improve HDL efficacy or as drug-delivery agents with therapeutic potential. In this paper, we first provide an overview of the molecules known to be transported by HDL particles and mainly discuss their functions in the cardiovascular system. Second, we describe the impact of cardiovascular risk factors and co-morbidities on HDL remodeling. Finally, we review the currently developed HDL-based approaches.
Highlights
High-density lipoproteins (HDL) represent a variety of lipoproteins with mean size of 8–10 nm and density of 1.063–1.21 g/mL [1]
There are two metabolic pathways involved in HDL-cholesteryl ester clearance, which include a direct uptake by the liver or by steroidogenic tissues via the scavenger receptor BI (SR-BI); and, the transfer to apoB-containing lipoproteins by the plasma protein cholesteryl ester transfer protein (CETP)
We have recently demonstrated that HDL remodeling is affected by low-density lipoprotein (LDL)-cholesterol levels
Summary
High-density lipoproteins (HDL) represent a variety of lipoproteins with mean size of 8–10 nm and density of 1.063–1.21 g/mL [1]. Triglyceride-enriched HDL particles are, in turn, susceptible to lipolytic modification by hepatic and endothelial lipases. Upon change by these two enzymes, the consequent smaller HDL particle becomes more sensitive to undergo faster catabolism [7]. HDL becomes the primary vehicle for the transport of cholesterol from peripheral cells to the liver for excretion and catabolism. During this complex metabolic process, molecules other than lipids (i.e., hormones, vitamins, proteins, and miRNAs) are known to be incorporated into HDL particles and transported to distal organs, likely contributing to maintaining cardiovascular health. We will first provide an overview of the molecules known to be transported by HDL particles and discuss the functions they are considered to regulate, describe the impact of cardiovascular risk factors and co-morbidities on HDL remodeling, and eventually review the HDL-based approaches developed so far
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