Abstract 498: HDL Containing Specific Proteins Blunts The Association With Cholesterol Efflux Capacity: Observations From The Dallas Heart Study

Abstract

Cholesterol efflux (CE) is a major athero-protective function of high density lipoproteins (HDL). HDL is a heterogeneous mixture of lipoproteins that contain apoA1, the prime protein of HDL, and may contain one or more of >200 other proteins. These other proteins cluster on subpopulations of HDL particles to form HDL subspecies. It is not entirely clear by simply measuring individual protein abundances what drives HDL function. We aimed to study the differential association of 7 HDL subspecies defined by presence or absence of a functional protein with extreme and persistent cholesterol efflux capacity (CEC). From ~3000 individuals in the multi-ethnic population-based DHS (Dallas Heart Study) cohort, people at the bottom 10% and top 90% of CEC were reassessed after 15 years resulting in 36 participants with extreme persistent high or low CEC for the present study. HDL with and without 7 individual proteins potentially relevant to HDL function were quantified using ELISA. Differences in association with CEC between HDL subspecies that contain or lack a defining protein were examined by heterogeneity test. In the low CEC group, HDL lacking apolipoprotein C3 (apoC3), complement C3, apoE (apolipoprotein E) and PLMG (plasminogen) were each associated positively with CEC while HDL subspecies containing these proteins were not positively associated with CEC. (Pearson correlation coefficient range 0.55369 to 0.66562 vs -0.08432 to -0.25198; p <0.05 for heterogeneity). In the high CEC group, no significant heterogeneity was found in association with CEC between HDL subspecies that contain or lack the same proteins. In people with extreme and persistent low CEC, HDL subspecies containing apoC3, complement C3, apoE and PLMG blunt the overall positive association between HDL and CEC. Our findings suggest that CEC of HDL in individuals with persistent and extreme low CEC is determined by the presence/absence of apoC3, complement C3, apoE and PLMG in HDL subspecies. Future studies involving manipulation of these proteins in HDL to investigate the effect on CE will provide deeper insight into functional speciation of HDL. This knowledge can be further applied to define biomarkers for altered CE in atherosclerotic cardiovascular diseases (ASCVD).