Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

Abstract

Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases.

Endothelial microparticles delivering microRNA-155 into T lymphocytes are involved in the initiation of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation

“…The human umbilical vein endothelial cell line is a widely accepted and the most common endothelial cell in multiple vascular and autoimmune diseases studies [21, 22]. TNF-α, which participates in the initiating events that culminate in aGVHD as well as amplifies the disease process once established, is an important mediator and regulator of aGVHD and significantly increases before the appearance of aGVHD in patients undergoing allo-HSCT [23].…”

Microparticles as autoantigens in systemic lupus erythematosus

“…Since the refractive index of polystyrene beads is higher than that of MPs, size determination may be affected. Common MP phenotypes measured in plasma are platelet MPs (CD41, CD42a), endothelial‐MPs (CD146, CD144, CD62E) and leucocyte‐MPs (CD45, CD14, CD15, CD4) …”

“…50 Since the refractive index of polystyrene beads is higher than that of MPs, size determination may be affected. Common MP phenotypes measured in plasma are platelet MPs (CD41, CD42a), 51 endothelial-MPs (CD146, CD144, CD62E) 52 and leucocyte-MPs (CD45, CD14, CD15, CD4). 53 In the assay of MPs, the presence of surface PS is often used to identify particles by staining with annexin V or lactadherin ( Figure 2).…”

Endothelial microparticles prevent lipid‐induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress

“…MPs can also be released in small numbers under basal physiologic conditions ( 15 ). Our laboratory has focused, in particular, on 100–1000 nm microvesicles that are released from endothelial cells, which we describe as endothelial microparticles (EMPs) ( 16 – 20 ). Although eNOS has been identified on EMPs ( 21 ), there is no evidence that supports functional eNOS activity ( 22 ), which we now show for the first time.…”