Oxidized low-density lipoprotein-induced microparticles promote endothelial monocyte adhesion via intercellular adhesion molecule 1

Abstract

Oxidized low-density lipoprotein (oxLDL) accumulates early in atherosclerotic lesions and plays an important role in the progressive formation of atherosclerotic plaques. Endothelial derived microparticles (EMPs) form a heterogeneous population of <1-μm particles that shed from endothelial membranes upon activation. While EMPs are shown to be involved in atherosclerotic pathophysiology and progression, there is no report regarding the relationship between oxLDL and EMPs. In this study, we aim to determine the influence of oxLDL on endothelial microparticle release and the subsequent regulation of the endothelial activation. EMPs were collected from the medium of human umbilical vein endothelial cells (HUVECs) treated with oxLDL or PBS as control. We find that oxLDL increases the release of EMPs containing intercellular adhesion molecule 1 (ICAM-1) but not vascular cell adhesion molecule 1 (VCAM-1). Confocal microscopy analysis further demonstrates that these EMPs interact with endothelial cells and increase the expression of ICAM-1 in HUVECs. The fact that injecting oxLDL-induced EMPs via the tail vein of ICR mice augments ICAM-1 expression on aortic endothelial cells confirms our results in vivo. Finally, oxLDL-induced EMPs from HUVECs increase the adhesion of monocytes to endothelial cells as determined by the adhesion assay. Our study suggests that oxLDL may augment the release of EMPs harboring increased levels of ICAM-1 that can be transferred to endothelial cells elsewhere. This leads to increased monocyte recruitment in other regions where oxLDL accumulation was initially more limited. EMPs may therefore serve as the mediator that propagates oxLDL-induced endothelial inflammation.

Oxidized low‐density lipoprotein in inflammation‐driven thrombosis

“…In either case, the effects of OxLDL on the release of MVs by platelets in vivo remain to be elucidated. Stimulation of ECs with OxLDL has also been found to trigger the release of MVs, which, in turn, induce the expression of ICAM-1 and promote monocyte adhesion to ECs [82]. However, a direct procoagulatory role for OxLDL-induced ECderived MVs still needs to be established.…”

Extracellular vesicles in atherothrombosis and cardiovascular disease: Friends and foes

“…1 and summarized in Table 1. Indeed, stimulation of EC with oxidised LDL (ox-LDL) particles can trigger the release of intercellular CAM (ICAM)-1-rich EV that can be transferred to other EC promoting monocyte adhesion [36]. Furthermore, a number of studies have reported that pro-inflammatory molecules can stimulate the release of leukocyte-derived EV that target EC and promote the recruitment of other leukocytes, feedback looping this process [37][38][39][40][41].…”

Cross-Talk between Lipoproteins and Inflammation: The Role of Microvesicles

“…It has been shown that oxLDL, in a time-and dose-dependent manner, promotes the in vitro release of endothelial MV rich in intercellular adhesion molecule 1 (ICAM-1) [63], which can be transferred from MV to endothelial cells increasing monocyte adhesion to endothelial cells [64], further propagating the atheroprone effects of oxLDL even in its absence. Moreover, enrichment of THP-1 monocytic cells with unsterilized cholesterol resulted in increased MV production [65], and these MV induced extensive leukocyte rolling and adherence to the endothelium.…”