Lecithin cholesterol acyltransferase: an anti- or pro-atherogenic factor?

Abstract

Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanistically link LCAT with cardiovascular disease. Imaging studies of patients with LCAT deficiency have also not yielded a clear answer to the role of LCAT in atherosclerosis. Recombinant LCAT, however, is currently being developed as a therapeutic product for enzyme replacement therapy of patients with genetic disorders of LCAT for the prevention and/or treatment of renal disease, but it may also have value for the treatment of acute coronary syndrome.

Fig. 1

A model of steps in the reverse cholesterol transport pathway. Step 1, Hepatic and intestinal synthesis of apolipoprotein A-I (apoA-I) and its association with phospholipids and cholesterol by the ATP-bindind cassette A1 (ABCA1) transporter forming nascent pre-β high-density lipoprotein (HDL). Step 2, Efflux of cholesterol from peripheral tissues by ABCA1 and ABCG1 transporters. Step 3, Esterification of cholesterol in HDL by lecithin cholesterol acyl transferase (LCAT) and transformation of nascent HDL into spherical α-HDL. Step 4, Cholesteryl ester transfer protein (CETP)-mediated and phoshpholipid transfer protein (PLTP)-mediated exchange of cholesteryl ester and phospholipids between HDL and low-density lipoprotein (LDL). Step 5, Hepatc uptake of cholesterol from HDL by scavenger receptor B type I (SR-BI) and from LDL by LDL receptor. LPL—lipoprotein lipase; VLDL—very low-density lipoprotein