Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype.
BACKGROUND
Epidemiological studies have shown that low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risk of cardiovascular disease, but the mechanisms for the possible atheroprotective effects of HDL cholesterol have still not been fully clarified, in particular in relation to clinical studies.


OBJECTIVE
To examine the inflammatory, anti-oxidative and metabolic phenotype of subjects with low plasma HDL cholesterol levels.


RESULTS
Fifteen subjects with low HDL cholesterol levels (eleven males and four females) and 19 subjects with high HDL (three males and 16 females) were recruited. Low HDL cholesterol was defined as ≤10th age/sex specific percentile and high HDL-C was defined as ≥90 age/sex specific percentile. Inflammatory markers in circulation and PBMC gene expression of cholesterol efflux mediators were measured. Our main findings were: (i) subjects with low plasma HDL cholesterol levels were characterized by increased plasma levels of CRP, MMP-9, neopterin, CXCL16 and ICAM-1 as well as low plasma levels of adiponectin, suggesting an inflammatory phenotype; (ii) these individuals also had reduced paraoxonase (PON)1 activity in plasma and PON2 gene expression in peripheral blood mononuclear cells (PBMC) accompanied by increased plasma levels of oxidized LDL suggesting decreased anti-oxidative capacity; and (iii) PBMC from low HDL subjects also had decreased mRNA levels of ABCA1 and ABCG1, suggesting impaired reverse cholesterol transport.


CONCLUSIONS
Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype that could contribute to the increased risk of atherosclerotic disorders in these subjects with low HDL levels.
Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway ; Faculty of Medicine, University of Oslo, Oslo, Norway.
Kirsten B
KB
Holven
Kjetil
K
Retterstøl
Thor
T
Ueland
Stine M
SM
Ulven
Marit S
MS
Nenseter
Marit
M
Sandvik
Ingunn
I
Narverud
Knut E
KE
Berge
Leiv
L
Ose
Pål
P
Aukrust
Bente
B
Halvorsen
D064286:ATP Binding Cassette Transporter 1 / Q000097:blood; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000097:blood; D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D001693:Biological Transport, Active; D002097:C-Reactive Protein / Q000378:metabolism; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D010084:Oxidation-Reduction; D010641:Phenotype; D051116:Receptors, Scavenger / Q000097:blood
C577836:ABCA1 protein, human; C419353:ABCG1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D019798:Neopterin; D002097:C-Reactive Protein; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9