Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins

Atherosclerosis. 2015 Aug;241(2):463-70. doi: 10.1016/j.atherosclerosis.2015.06.003. Epub 2015 Jun 6.

Abstract

Objective: Clusterin/apolipoprotein J (apoJ) circulates in blood in part associated to lipoproteins or in unbound form. When bound to HDL, apoJ is antiatherogenic by inhibiting endothelial cell apoptosis; thus, any factor modifying apoJ association to HDL would decrease its antiatherogenic function. However, the exact distribution of apoJ in each lipoprotein fraction, or in lipoprotein-non bound form has not been specifically investigated either in normolipemia or in dyslipemia.

Methods: Basic lipid profile and apoJ concentration were determined in sera from 70 subjects, including a wide range of cholesterol and triglyceride concentrations. Lipoproteins were isolated by ultracentrifugation and their lipid and apolipoprotein composition was assessed.

Results: In the overall population, serum apoJ positively associated with cholesterol, triglyceride and VLDL-C concentrations, and HDL-C and triglyceride were independent predictors of increased apoJ concentration. Approximately, 20.5% of circulating apoJ was associated with lipoproteins (18.5% HDL, 0.9% LDL and 1.1% VLDL) and 79.5% was not bound to lipoproteins. Serum apoJ concentration was higher in hypercholesterolemic (HC), hypertriglyceridemic (HTG) and combined hyperlipidemic (CHL) sera compared to normolipemic (NL) sera (HC, 98.15 ± 33.6 mg/L; HTG, 103.3 ± 36.8 mg/L; CHL, 131.7 ± 26.8 mg/L; NL, 66.7 ± 33.8 mg/L; P < 0.001). ApoJ distribution was also altered in hyperlipidemia; approximately 30% of circulating apoJ was associated to lipoproteins in the NL group whereas this proportion rounded 15% in hyperlipidemic subjects.

Conclusions: Our findings indicate that hyperlipidemia increases the concentration of apoJ in serum but, in turn, the content of lipoprotein-associated apoJ decreases. The redistribution of apoJ in hyperlipidemia could compromise the antiatherogenic properties of HDL.

Keywords: Apolipoprotein J; Atherosclerosis; Cardiovascular risk factors; Hyperlipidemia; Lipoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein C-III / metabolism
  • Cholesterol / blood
  • Clusterin / blood*
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hyperlipidemias / blood*
  • Lipids / blood
  • Lipoproteins / blood*
  • Lipoproteins / metabolism
  • Lipoproteins, VLDL / blood
  • Male
  • Middle Aged
  • Risk Factors
  • Triglycerides / blood

Substances

  • Apolipoprotein C-III
  • CLU protein, human
  • Clusterin
  • Lipids
  • Lipoproteins
  • Lipoproteins, VLDL
  • Triglycerides
  • Cholesterol