185 - High lysophosphatidylcholine and low phosphatidylcholine concentrations in HDL phospholipids are associated with atherosclerosis in relation to decreased cholesterol efflux capacity (ID 173)
Abstract
Background and Aims
Cholesterol efflux capacity (CEC) may be a more important risk marker than plasma HDL cholesterol levels. However, developing a standardized clinical laboratory test for measuring CEC would be extremely difficult because cell lines and pooled plasma are specific to each institution. The aim of this cross-sectional study was to identify phospholipid (PL) components of HDL, which are predictive of both decreased CEC and atherosclerosis severity, in order to develop novel standardized biomarkers as alternatives to CEC.
Methods
The study enrolled 385 consecutive patients (mean age 49±15, 188 women (49%)), among them 111 (29%) with atherosclerotic cardiovascular disease (ASCVD). We measured individual CEC from 3H-cholesterol-labelled J774.1 cells, total PL, phosphatidylcholine (PC), lysoPC (LPC), and sphingomyelin (SM) using apolipoprotein B-depleted plasma. PC/PL, LPC/PL and SM/PL percentages were adopted to indicate HDL-PL composition.
Results
Decreased PC/PL, increased LPC/PL, and increased SM/PL percentagesratio were associated with decreased CEC. However, only decreased PC/PL and increased LPC/PL were independently related with advanced carotid atherosclerosis and the presence of ASCVD in multivariate analyses adjusted for traditional cardiovascular risk factors.
Conclusions
Increased LPC and decreased PC in HDL-PL were associated with atherosclerosis in relation to decreased CEC, suggesting the involvement of lipoprotein-associated phospholipase A2 (LP-PLA2) in HDL quality. Therefore, further studies are needed to elucidate how LP-PLA2 or LPC reduces CEC. Additionally, since CEC measurements varied among patients with comparable HDL-PL compositions, determination of fatty acyl compositions of LPCs and PCs using lipidomic analysis would be more informative when searching for novel therapeutic targets.
