Lecithin: cholesterol acyltransferase--from biochemistry to role in cardiovascular disease

Abstract

Purpose of review: We discuss the latest findings on the biochemistry of lecithin : cholesterol acyltransferase (LCAT), the effect of LCAT on atherosclerosis, clinical features of LCAT deficiency, and the impact of LCAT on cardiovascular disease from human studies.

Recent findings: Although there has been much recent progress in the biochemistry of LCAT and its effect on high-density lipoprotein metabolism, its role in the pathogenesis of atherosclerosis is still not fully understood. Studies from various animal models have revealed a complex interaction between LCAT and atherosclerosis that may be modified by diet and by other proteins that modify lipoproteins. Furthermore, the ability of LCAT to lower apoB appears to be the best way to predict its effect on atherosclerosis in animal models. Recent studies on patients with LCAT deficiency have shown a modest but significant increase in incidence of cardiovascular disease consistent with a beneficial effect of LCAT on atherosclerosis. The role of LCAT in the general population, however, has not revealed a consistent association with cardiovascular disease.

Summary: Recent research findings from animal and human studies have revealed a potential beneficial role of LCAT in reducing atherosclerosis but additional studies are necessary to better establish the linkage between LCAT and cardiovascular disease.

Figures

Figure 1. Diagram of the Reverse Cholesterol Transport Pathway

Pre-beta HDL produced, as a consequence of the interaction of apoA-I with the ABCA1 transporter on the liver, obtains additional phospholipid and cholesterol from ABCA1 transporters on peripheral cells, such as macrophages. In addition, HDL can acquire more lipid by other mechanisms, such as from the ABCG1 transporter, the SR-BI receptor or by an aqueous diffusion process. Cholesterol removed from cells by HDL is converted to cholesteryl esters by LCAT, which transforms pre-beta HDL to alpha-HDL. Cholesterol can be directly returned to the liver after uptake by the SR-BI receptor or after transfer to apoB-containing lipoproteins by CETP. Phospholipid transfer protein (PLTP) and hepatic lipase (HL) promote the interconversion alpha-HDL and pre-beta HDL.

Figure 2. Diagram of the LCAT Reaction

LCAT cleaves the fatty acid (R2) from the sn-2 position of phosphatidylcholine and then transesterifies it to the A-ring of cholesterol, producing lysophosphatidylcholine and cholesteryl ester.