Association of small dense LDL serum levels and circulating monocyte subsets in stable coronary artery disease

PLoS One. 2015 Apr 7;10(4):e0123367. doi: 10.1371/journal.pone.0123367. eCollection 2015.

Abstract

Objective: Atherosclerosis is considered to be an inflammatory disease in which monocytes and monocyte-derived macrophages play a key role. Circulating monocytes can be divided into three distinct subtypes, namely in classical monocytes (CM; CD14++CD16-), intermediate monocytes (IM; CD14++CD16+) and non-classical monocytes (NCM; CD14+CD16++). Low density lipoprotein particles are heterogeneous in size and density, with small, dense LDL (sdLDL) crucially implicated in atherogenesis. The aim of this study was to examine whether monocyte subsets are associated with sdLDL serum levels.

Methods: We included 90 patients with angiographically documented stable coronary artery disease and determined monocyte subtypes by flow cytometry. sdLDL was measured by an electrophoresis method on polyacrylamide gel.

Results: Patients with sdLDL levels in the highest tertile (sdLDL≥4mg/dL;T3) showed the highest levels of pro-inflammatory NCM (15.2±7% vs. 11.4±6% and 10.9±4%, respectively; p<0.01) when compared with patients in the middle (sdLDL=2-3mg/dL;T2) and lowest tertile (sdLDL=0-1mg/dL;T1). Furthermore, patients in the highest sdLDL tertile showed lower CM levels than patients in the middle and lowest tertile (79.2±8% vs. 83.9±7% and 82.7±5%; p<0.01 for T3 vs. T2+T1). Levels of IM were not related to sdLDL levels (5.6±4% vs. 4.6±3% vs. 6.4±3% for T3, T2 and T1, respectively). In contrast to monocyte subset distribution, levels of circulating pro- and anti-inflammatory markers were not associated with sdLDL levels.

Conclusion: The atherogenic lipoprotein fraction sdLDL is associated with an increase of NCM and a decrease of CM. This could be a new link between lipid metabolism dysregulation, innate immunity and atherosclerosis.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / analysis*
  • Coronary Angiography
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / pathology*
  • Cross-Sectional Studies
  • Female
  • Flow Cytometry
  • Humans
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Monocytes / pathology*

Substances

  • Biomarkers
  • Lipoproteins, LDL

Grants and funding

This work was supported by the FWF Austrian Science Fund, Grant Number SFB-54, Cellular Mediators Linking Inflammation and Thrombosis (Vienna, Austria), the Association for the Promotion of Research on Arteriosclerosis, Thrombosis and Vascular Biology (Vienna, Austria) and the Ludwig Boltzmann Cluster for Cardiovascular Research (Vienna, Austria). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.