Association of Small Dense LDL Serum Levels and Circulating Monocyte Subsets in Stable Coronary Artery Disease

Abstract

ObjectiveAtherosclerosis 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.MethodsWe 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.ResultsPatients 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.ConclusionThe 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.

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

“…Several studies indicated a direct role of sdLDL in atherogenesis and provided solid evidence that the role of sdLDL goes beyond a simple marker of metabolic disorder. These particles exhibit reduced binding capacities to LDL-receptors and show a stronger affinity to the extracellular matrix within the vascular wall [37,38]. Consistent with these findings, a significant difference in LDL-C levels was also observed between subjects with subclinical atherosclerosis and those without in the present study, however, the lack of sdLDL determination is a limitation of the study.…”

Uremic Toxicity-Induced Eryptosis and Monocyte Modulation: The Erythrophagocytosis as a Novel Pathway to Renal Anemia

“…+ monocytes have a pro-inflammatory profile in blood as activated-macrophages in connective tissue, and their proportion is expanded in various infectious and inflammatory diseases [6,9,21] . We observed not only a higher proportion of CD14 ++ /CD16 + in patients with pre-dialysis CKD and HD patients compared to controls, but also that this differentiation may be induced by exposure to uremic sera, and sera from advanced CKD stages promoted a more substantial shift toward the CD14 ++ /CD16 + profile.…”

“…+ is substantially increased in inflammatory conditions [6,8,9] , including CKD [8] and has been linked to cardiovascular complications in hemodialysis (HD) and non-dialysis CKD patients [10,11] . However, processes underlying the functional shift toward blood CD14 ++ /CD16 + monocytes in CKD remain elusive.…”

Associations of apolipoprotein B/apolipoprotein A-I ratio with pre-diabetes and diabetes risks: a cross-sectional study in Chinese adults

“…Hence, it is not unexpected that the ApoB/ApoA-I ratio was closely related with TG, TC, HDL-C and LDL-C. Apolipoprotein B and A-I are the major protein moieties of LDL and HDL, respectively. The level of ApoB reflects the number of potentially atherogenic particles 17. Meanwhile, ApoA-I plays an important role in removing excess cholesterol from tissues and incorporating it into HDL for reverse transport to the liver, forming the basis for atheroprotective events 18…”