The negative effect of ANGPTL8 on HDL-mediated cholesterol efflux capacity

Mengdie Luo1, Ziyu Zhang1, Yani Peng2

  • 1Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, No.139, Middle Renmin Road, Changsha, 410011, Hunan, China.

Cardiovascular Diabetology
|November 10, 2018
PubMed
Abstract

Insights

Angiopoietin-like protein 8 (ANGPTL8) negatively impacts high-density lipoprotein (HDL) function by reducing cholesterol efflux capacity. This finding suggests a novel pathway through which ANGPTL8 influences lipid metabolism and atherosclerosis progression.

Area of Science:

  • Lipid metabolism research
  • Cardiovascular disease mechanisms
  • Biomarker discovery

Background:

  • Angiopoietin-like protein 8 (ANGPTL8) is known to affect lipid metabolism by inhibiting lipoprotein lipase, increasing plasma triglyceride levels.
  • The precise mechanisms by which ANGPTL8 influences lipid metabolism, particularly its effects on high-density lipoprotein (HDL) function, remain incompletely understood.
  • HDL plays a crucial role in protecting against atherosclerosis progression, making its functional integrity a key area of research.

Purpose of the Study:

  • To investigate the impact of ANGPTL8 on the functional capacity of HDL.
  • To explore potential novel pathways through which ANGPTL8 affects lipid metabolism.
  • To determine the relationship between ANGPTL8 levels and HDL-mediated cholesterol efflux capacity in subjects with and without coronary artery disease (CAD) and diabetes mellitus (DM).

Main Methods:

  • Recruitment of 210 subjects for the study.
  • Quantification of plasma ANGPTL8 levels using enzyme-linked immunosorbent assays (ELISAs).
  • Measurement of cholesterol efflux capacity, a key biomarker of HDL function, using a H³-cholesterol loading THP-1 cell model.

Main Results:

  • Plasma ANGPTL8 levels were significantly higher in individuals with diabetes mellitus (DM) compared to those without DM.
  • Subjects with CAD and DM exhibited significantly reduced cholesterol efflux capacity compared to controls.
  • A significant inverse correlation was observed between plasma ANGPTL8 levels and cholesterol efflux capacity (r = -0.188, P < 0.01).
  • Regression analysis identified plasma ANGPTL8 as an independent contributor to reduced cholesterol efflux capacity (standardized β = -0.143, P = 0.023).

Conclusions:

  • ANGPTL8 exerts a negative influence on HDL-mediated cholesterol efflux capacity.
  • This finding suggests a novel mechanism by which ANGPTL8 contributes to dyslipidemia and potentially atherosclerosis.
  • Further research is warranted to elucidate the therapeutic implications of targeting ANGPTL8 for cardiovascular health.

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