Endocrinol Metab.  2016 Jun;31(2):223-229. 10.3803/EnM.2016.31.2.223.

High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

• Ossoli A
• Pavanello
• Calabresi

• KMID: 2308851
• DOI: http://doi.org/10.3803/EnM.2016.31.2.223

Abstract

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.

Keyword

Lipoproteins, HDL; Lecithin:cholesterol acyltransferase; Atherosclerosis

MeSH Terms

Animals
Atherosclerosis*
Cholesterol*
Coronary Disease
Humans
Incidence
Lecithins*
Lipoproteins*
Lipoproteins, HDL
Liver
Macrophages
Plasma
Sterol O-Acyltransferase*
Cholesterol
Lecithins
Lipoproteins
Lipoproteins, HDL
Sterol O-Acyltransferase

Figure

• 

  Fig. 1 High-density lipoprotein (HDL) metabolism. HDL are a heterogeneous lipoprotein family and plasma interconversion within different subclasses is due to action of various enzymes. Lecithin:cholesterol acyltransferase (LCAT) esterifies free cholesterol located on the surface of pre-β-HDL. The cholesterol esters generated by LCAT activity are more hydrophobic than free cholesterol and they migrate into the hydrophobic core of the lipoprotein, with the resulting conversion of pre-β-HDL into α-HDL3. The α-HDL3 produced by LCAT interact with cholesteryl ester transfer protein (CETP), that exchanges cholesteryl esters for triglycerides generating large cholesteryl ester-poor and triglyceride-rich HDL particles (α-HDL2). α-HDL2 can be converted back to pre-β-HDL through a variety of lipases activities that hydrolyze triglycerides and phospholipids on HDL. CE, cholesteryl esters; TG, triglyceride; HL, hepatic lipase; EL, endothelial lipase; PLTP, phospholipid transfer protein.

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