Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

Abstract

High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.

Keywords: HDL-C; lipoproteins; paraoxonase; polyphenols.

Figure 1

Classes and composition of lipoproteins. The classification criterion is based on the flotation density of the lipoproteins, the proportion of the different lipids and apolipoproteins, and the diameter of the particle. Chylomicrons (CM) are large, triglyceride-rich, and made in the enterocytes. The removal of triglycerides from very low-density lipoproteins (VLDL) results in the formation of intermediate-density lipoprotein (IDL) particles which are enriched in cholesterol and triglycerides and are pro-atherogenic. Low-density lipoproteins (LDL) are enriched only in cholesterol and are the most pro-atherogenic particles. High-density lipoproteins (HDL) are smaller than the other lipoproteins and enriched mainly in proteins. TG = triglycerides; PHO = phospholipids; Apo = apolipoprotein.

Figure 2

Cardioprotective function of HDL. The main cardioprotective properties of HDL include the inhibition of the oxidation of LDL (ox-LDL) through the activity of paraoxonase 1 (PON1) and the transport of antioxidant molecules, the inhibition of the expression of adhesion molecules in inflammatory processes and the efflux of cholesterol, decreasing the endothelial dysfunction. IL = interleukin; TNF = tumor necrosis factor; ROS = reactive oxygen species. VCAM-1 = vascular cell adhesion molecule 1; ICAM-1 intercellular adhesion molecule 1.

Figure 3

Biogenesis and catabolism (reverse cholesterol transport) of high-density lipoproteins. ABCA1 = ATP binding cassette subfamily A member 1; ApoAl = apolipoprotein Al; ApoE = apolipoprotein E; CE = cholesterol ester; CETP = cholesteryl ester transfer protein; FFA = free fatty acids; LCAT = lecithin-cholesterol acyltransferase; LDL = low density lipoprotein; LDLr = LDL receptor LPL = lipoprotein lipase; PLTP = phospholipid transfer protein; SR-B1 = scavenger receptor class B member 1; Tg = triglycerides; VLDL = very low-density lipoprotein.