title: Increased concentration of clusterin/apolipoprotein J (apoJ) in hyperlipemic serum is paradoxically associated with decreased apoJ content in lipoproteins.
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.
authors.affiliation: Cardiovascular Biochemistry Group, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.affiliation: Cardiovascular Biochemistry Group, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Martínez-Bujidos
authors.affiliation: Cardiovascular Biochemistry Group, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pérez-Cuellar
authors.affiliation: Endocrinology and Nutrition Department, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pérez
authors.affiliation: Cardiovascular Biochemistry Group, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
authors.affiliation: Cardiovascular Biochemistry Group, Biomedical Research Institute, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain. Electronic address: jsanchezq@santpau.cat.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Sánchez-Quesada
mesh_terms: D000328:Adult; D000368:Aged; D053305:Apolipoprotein C-III / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D051152:Clusterin / Q000097:blood*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D053305:Apolipoprotein C-III; C495242:CLU protein, human; D051152:Clusterin; D008055:Lipids; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol
keywords: Apolipoprotein J; Atherosclerosis; Cardiovascular risk factors; Hyperlipidemia; Lipoproteins