Do neutrophil microvesicles affect atherosclerotic plaque erosion?

Atherosclerosis is a major cause of death and imparts a significant burden on health services globally. It is characterised by the development of lesions in the artery called plaques. As these plaques develop, they can impede blood flow to the heart resulting in symptoms of angina and in some cases trigger rapid blood clotting, called thrombosis, which can partially or fully occlude the artery lumen, manifesting in myocardial infarction. Historically research has focused primarily on atherosclerosis caused by lipid-rich and highly inflammatory plaques with a thin fibrous cap which is prone to rupture. However, more recently the importance of a second form of plaque, characterised by a lower lipid content, fewer inflammatory cells and a thick fibrous cap, has garnered more interest. These plaques do not cause thrombosis via plaque rupture but rather the endothelium of the plaque progressively erodes until thrombosis occurs. This process is referred to as plaque erosion. As the proportion of major cardiac events accounted for by erosion increases, largely as a result of improved treatments targeting the cause of plaque rupture whilst being ineffective in the management of erosion research interest has intensified. Neutrophils have recently been implicated in plaque erosion through the induction of endothelial cell dysfunction. Neutrophils produce 0.1-1µm microvesicles from their cell membrane and these neutrophil microvesicles have been linked with atherosclerotic plaque progression. In this study I investigated the hypothesis that NMVs affect plaque erosion through driving endothelial cell dysfunction. Several techniques were used to investigate the effect of neutrophil microvesicles on primary human coronary artery endothelial cells and platelet function. Neutrophils and platelets were isolated from whole blood from healthy volunteers and neutrophils stimulated to generate neutrophil microvesicles. Human coronary artery endothelial cells were cultured under static and atheroprone flow conditions on varying extracellular matrix components found within eroded plaques to model the environment of an eroded plaque.