Abstract

Cardiovascular disease (CVD) is the leading cause of death globally. For close to four decades, we have known that high density lipoprotein (HDL) levels are inversely correlated with the risk of CVD. HDL is a complex particle that consists of proteins, phospholipids, and cholesterol and has the ability to carry micro-RNAs. HDL is constantly undergoing remodelling throughout its life-span and carries out many functions. This review summarizes many of the different aspects of HDL from its assembly, the receptors it interacts with, along with the functions it performs and how it can be altered in disease. While HDL is a key cholesterol efflux particle, this review highlights the many other important functions of HDL in the innate immune system and details the potential therapeutic uses of HDL outside of CVD.

Highlights

  • Cardiovascular disease (CVD) remains the dominant cause of death globally [1], and while it is recognized as a multifactorial disease with many risk factors, atherosclerosis is responsible for the major pathology contributing to end stage heart disease [2]

  • While the precise mechanism for PON-1 binding to high density lipoprotein (HDL) is not completely understood, it is suggested that HDL mediates the release of PON-1 from the plasma membranes of cells as incubation of PON-1 transfected cells with HDL caused a significant increase in the media activity of the enzyme and a decrease in cell-surface activity compared to PON-1 cells alone [64]

  • PON-1 plays an important role in the anti-inflammatory properties of HDL, where it functions as an antioxidant, preventing the oxidation of atherogenic lipoproteins such as low density lipoprotein (LDL)

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Summary

Introduction

Cardiovascular disease (CVD) remains the dominant cause of death globally [1], and while it is recognized as a multifactorial disease with many risk factors, atherosclerosis is responsible for the major pathology contributing to end stage heart disease [2]. Dyslipidemia, or the imbalance of plasma lipid levels, together with disturbances of intracellular lipid metabolism, underlie atherosclerotic plaque development. Such dyslipidemias include increases in both plasma total and low density lipoprotein (LDL) cholesterol leading to LDL modification and increased accumulation of modified LDL in the intima of the vasculature. We have come to understand that for every 5 mg/dL decease in HDL levels below the average (∼50 mg/dL), there is an approximate 25% increase in the risk of myocardial infarction [3]. Perhaps the most seminal finding of recent times relating to this is the work from Dr Rader’s laboratory which clearly showed that HDL function (i.e., the ability to promote cholesterol efflux from a standardized cell model) was impaired from patients with CVD and was a leading predictor of risk [5]. It is imperative that HDL composition and function in normal and disease states is comprehensively understood

Atherosclerosis and Lipids: A Brief Overview
High Density Lipoprotein
Lecithin
HDL Cargo
Cholesterol Efflux and the Formation of HDL
Receptors Involved in Cholesterol Efflux
Anti-Inflammatory Effects of HDL
High Density Lipoproteins in Disease
Findings
Perspective
Full Text
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