Association of lecithin-cholesterol acyltransferase activity and low-density lipoprotein heterogeneity with atherosclerotic cardiovascular disease risk: a longitudinal pilot study

Abstract

BackgroundLecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. However, recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size. The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size.MethodsThe subjects were a total of 335 patients, derived from our previous study cohort, with one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). For this study, we measured the LDL-particle size (relative LDL migration [LDL-Rm value]) by polyacrylamide gel electrophoresis in the subjects, along with the changes in the LCAT activity, at the end of a follow-up period of at least 1 year.ResultsThe results revealed that the absolute change (Δ) in the LDL-particle size increased significantly as the quartile of Δ LCAT activity increased (p = 0.01). A multi-logistic regression adjusted-analysis revealed that Δ LCAT activity in the fourth quartile as compared to that in the first quartile was independently predictive of an increased LDL-particle size (odds ratio [95% confidence interval]: 2.03 [1.02/4.04], p = 0.04). Moreover, the ∆ LCAT activity was also positively correlated with ∆ TRL-related markers (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein B, apolipoprotein C-2, and apolipoprotein C-3).ConclusionsThe results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in the LDL-particle size in patients at a high risk for ASCVD. To reduce the risk of ASCVD, it may be important to focus not only on the quantitative changes in the serum LDL-cholesterol levels, but also on the LCAT activity.Trial registrationUMIN (https://upload.umin.ac.jp/cgi-bin/ctr/ctr_reg_list.cgi) Study ID: UMIN000033228 retrospectively registered 2 July 2018.

Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach

“…All of these activities were involved in the regulation and uptake of cholesterol, and reverse cholesterol transport. High level of phosphatidylcholine-sterol O -acyltransferase or LCAT might be associated with decrease in LDL particle size, and increase in TRL markers in CVD patients 67 , 68 . Our data suggest that the GA genotype has high LCAT activity, as compared to the GG genotype and may have less atherogenic risk in terms of LCAT related genes.…”

An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

“…Higher LCAT activity is correlated with insulin resistance and nonalcoholic fatty liver disease [ 126 ]. The LDL-particle size can be reduced and positively associated with atherosclerotic cardiovascular disease [ 127 ]. However, in some cases, increased LCAT levels are associated with a reduced coronary atheroma burden [ 128 ].…”

Terminalia arjuna Bark Extract Reduces High Fat Diet Induced Cardiac Damage in Wistar Rats by Altering Biochemical and Histological Parameters

“…This fairly indicates that measurement of LCAT activity is useful for predicting atherosclerotic cardiovascular disease (ASCVD) in patients at a high risk for progression of atherosclerosis. 35 Aqueous extract of T. arjuna showed protective action against alcohol induced hepatic and renal injury by ameliorating both the nitrosative and oxidative stress by enhancing the antioxidant status of the system. 36 In alcohol linduced, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were evaluated in liver and kidney.…”