Endothelial Microparticles

Even under normal physiological conditions, individuals and endothelial cells continuously shed small, cell membrane-enclosed vesicles, carrying many cytoplasmic as well as surface markers, especially adhesion molecules deprived from “parent” or originating cells. These particles (diameters in the range of 0.1-1 pm) can be found either freely circulating in plasma bound to other blood components and are known as “endothelial microparticles” (EMPs). In addition to these many protein biomarkers that indicate their origin, microparticles (MPs) also exhibit phosphati- dylserine (PS) on the outer leaflets of their plasma membrane. PS exposed on the surface of EMP binds to annexin V and describes “apoptotic endothelial microparticles” [55]. Because of this, characteristic MPs were once thought to represent “apoptotic bodies.” However, MPs are now accepted to be a separate population of secreted vesicles. There has been increased research interest in deducing the function of MP release, whether it is adaptive and protective or damaging to the endothelial cells, and it still remains unclear. However, MPs may be a double-edged sword: although MP release is associated with various pathologies, inhibition of cellular MP release is associated with cell detachment and death [65]. When exposed to metabolic and inflammatory stress, such as in MS, endothelial cells release significantly more MPs, indicating the potential application of MPs as diagnostic marker and indices of disease severity and indicators of therapeutic response [66]. However, MPs are not only a marker (or a consequence) of MS but also pathological factors, contributing to the initiation and progression of disease activity [139]. Elevation in MP release is associated with a decline in BBB function and correlates with increase in leukocyte infiltration [67]. We found that blood-circulating MPs are not homogeneous but consist of several different species that show different patterns of release depending on disease states [68]. Although various EMPs, including CD31+ and CD54+ EMPs (EMPCD31+ and EMPCD54+), are high in active MS and decrease during therapy, EMPCD146+ did not show such correlation [66]. EMPs are also not the only type of MPs present in the blood. MPs can also be derived from other cells including platelets, erythrocytes, and leukocytes [55]. Platelet MPs (PMPs), which can activate thrombosis, are also elevated in MS and contribute to vascular injury [69], and such increased EMP can elevate extravasation of immune cells across the BBB by promoting monocyte adhesion and migration contributing to the pathogenesis of MS [70, 71].

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