High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol

Abstract

A key to effective treatment of cardiovascular disease is to understand the body’s complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [high-density lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT pathway consists of the following steps: 1. Cholesterol efflux from peripheral tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease.

The Effect of Haplotypes in the CETP and LIPC Genes on the Triglycerides to HDL-C Ratio and Its Components in the Roma and Hungarian General Populations

“…It is characterized by a low level of high-density lipoprotein cholesterol (HDL-C) and increased level of triglyceride (TG) [16]. The high-density lipoprotein is the key component involved in reverse cholesterol transport and the transfer of cholesteryl esters between lipoproteins [17]. The level of HDL-C is inversely associated with the risk of coronary heart diseases and is interpreted as a key indicator of predicting CVD risk [18].…”

Protective effect of vitamin C against theobromine induced hepatorenal and cardio toxicity in male albino Wistar rats

“…Measurement of the lipoprotein concentrations is useful in evaluating dangers posed on the cardiovascular system by any substance (Barter et al, 2007). High density lipoprotein cholesterol is involved in the transport of cholesterol from tissues to the liver while low density lipoprotein cholesterol is reported to aid in the deposition of cholesterol in extrahepatic tissues (Trajkovska and Topuzovska, 2017). Consequently, elevation of LDL-C has a negative impact on the cardiovascular system and could result in cardiovascular events such as arrythmia, cardiac arrest and heart attack (Dayuan and Mehta, 2005).…”

Peptides Obtained by Enzymatic Decomposition of Mackerel Prevent Nonalcoholic Steatohepatitis in Sprague-Dawley Rats fed a High-fat and High-cholesterol Diet

“…The reason for this result is unclear. Lecithin cholesterol acyltransferase (LCAT) is synthesized by the liver, and esterifies FC on the surface of HDL, forming cholesteryl esters [18]. Because the histological hepatic fibrosis was more progressive in the EMP5% group, it is conceivable that LCAT synthesis and esterification of FC can be stagnated.…”