Subjects with low plasma HDL cholesterol levels are characterized by an inflammatory and oxidative phenotype

PLoS One. 2013 Nov 11;8(11):e78241. doi: 10.1371/journal.pone.0078241. eCollection 2013.

Abstract

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.

Methods and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / blood
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / blood
  • Adult
  • Aged
  • Atherosclerosis / blood
  • Biological Transport, Active
  • C-Reactive Protein / metabolism
  • Chemokine CXCL16
  • Chemokines, CXC / blood
  • Cholesterol, HDL / blood*
  • Female
  • Humans
  • Inflammation / blood
  • Intercellular Adhesion Molecule-1 / blood
  • Lipoproteins, LDL / blood
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Neopterin / blood
  • Oxidation-Reduction
  • Phenotype*
  • Receptors, Scavenger / blood

Substances

  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • CXCL16 protein, human
  • Chemokine CXCL16
  • Chemokines, CXC
  • Cholesterol, HDL
  • Lipoproteins, LDL
  • Receptors, Scavenger
  • oxidized low density lipoprotein
  • Intercellular Adhesion Molecule-1
  • Neopterin
  • C-Reactive Protein
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This work was supported by grants from the Norwegian Association of Heart and Lung Patients, The Throne Holst Foundation for Nutrition Research, the Freia Chocolade Fabriks Medical Foundation, Johan H. Andresen Medical Foundation, University of Oslo, and the Nordic Center of Excellence (NCoE) “SYSDIET” by Nordforsk (070014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.