Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease

Abstract

Objective: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. Methods: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. Results: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. Conclusion: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.

Association of monocyte to HDL cholesterol level with contrast induced nephropathy in STEMI patients treated with primary PCI

“…Conversely, HDL-C has many athero-protective effects secondary to its reverse cholesterol transport, anti-inflammatory and antioxidant actions. Recent studies have shown a direct link between HDL and monocyte subgroups in patients with CAD and chronic renal disease [39][40][41]. In addition, HDL-C may impact the formation and activation of monocytes [42][43][44].…”

Nonclassical Patrolling Monocyte Function in the Vasculature

“…Percentage of nonclassical monocytes is also positively associated with small HDL levels 73 . Nevertheless, the association between nonclassical monocytes and atherosclerosis does not necessarily imply causality.…”

The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes

“…However, these properties varied in atherogenic dyslipidaemia, where small HDL particles were associated with the presence and severity of atherosclerotic disease. It was demonstrated that coronary artery disease (CAD) patients with elevated levels of small HDLs exhibited a shift towards pro‐inflammatory monocyte subset distribution as serum levels of small HDLs significantly correlated with the proportion of circulating non‐classical monocytes . The numbers of non‐classical monocytes were increased in hypercholesterolaemic patients with the ApoE4 allele as well as in healthy individuals with ApoE3/E4 or E4/E4 phenotype .…”