Extracellular vesicles in autoimmune vasculitis - Little dirts light the fire in blood vessels

Abstract

Systemic vasculitis is diverse group of autoimmune disorders which are characterized by inflammation of blood vessel walls with deep aching and burning pain. Their underlying etiology and pathophysiology still remain poorly understood. Extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, are membrane vesicular structures that are released either during cell activation, or when cells undergo programmed cell death, including apoptosis, necroptosis, and pyroptosis. Although EVs were thought as cell dusts, but now they have been found to be potently active since they harbor bioactive molecules, such as proteins, lipids, nucleic acids, or multi-molecular complexes. EVs can serve as novel mediators for cell-tocell communications by delivery bioactive molecules from their parental cells to the recipient cells. Earlier studies mainly focused on MVs budding from membrane surface. Recent studies demonstrated that EVs may also carry molecules from cytoplasm or even from nucleus of their parental cells, and these EVs may carry autoantigens and are important in vasculitis. EVs may play important roles in vasculitis through their potential pathogenic involvements in inflammation, autoimmune responses, procoagulation, endothelial dysfunction/damage, angiogenesis, and intimal hyperplasia. EVs have also been used as specific biomarkers for diagnostic use or disease severity monitoring. In this review, we have focused on the aspects of EV biology most relevant to the pathogenesis of vasculitis, discussed their perspective insights, and summarized the exist literature on EV relevant studies in vasculitis, therefore provides an integration of current knowledge regarding the novel role of EVs in systemic vasculitis.

Extracellular Thimet Oligopeptidase is Released with Extracellular Vesicles from Human Prostate Cancer Cells

“…Phosphotidylserine is a marker of EV generation 34 . The sizes of these membrane surface domains are consistent with the recognized size range for membrane microvesicles (approximately 0.1 to 1 µm) 26,27,35 . Thus, A23187 treatment appears to induce the budding and release of EV-associated TOP protein.…”

“…Extracellular vesicles (EVs) are small cellular membrane vesicles that are either released from intracellular space (exosomes) 27 , or budded from the plasma membrane surface of almost all cell types upon cell activation or programmed cell death (microvesicles) [23][24][25][26][27] . In the past several years, the biomedical research field has shown growing interest in the biological roles of EVs due to their emerging roles in pathophysiological conditions and various human diseases 26,27 . Studies show that EVs carry a heterogeneous array of intracellular and membrane-associated biologically active molecules, such as proteins, lipids, and DNA or RNA [23][24][25][26][27] .…”

“…In the past several years, the biomedical research field has shown growing interest in the biological roles of EVs due to their emerging roles in pathophysiological conditions and various human diseases 26,27 . Studies show that EVs carry a heterogeneous array of intracellular and membrane-associated biologically active molecules, such as proteins, lipids, and DNA or RNA [23][24][25][26][27] . Previous studies demonstrate that EVs carry transmembrane protease of the matrix metalloproteinase superfamily (MMP14) 23 .…”

Current State of Precision Medicine in Primary Systemic Vasculitides

“…EVs were defined in 1967 as "dust" from platelets (130). More recently, it has been shown that EVs are membrane vesicles that are released by almost all eukaryotic cells during cell activation and programmed cell death (131)(132)(133)(134). Heterogeneity of EVs is essential.…”

“…Heterogeneity of EVs is essential. They are classified into three groups with regard to biological features and their size: exosomes, microvesicles (MVs), and apoptotic bodies (132,133,135,136). EVs are responsible for immune regulation, cell-to-cell interaction, and signal transmission by transporting bioactive molecules including proteins and lipids, DNA, and various RNAs, such as mRNAs, small-interfering RNAs (siRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) and other molecules produced by cells (132,(137)(138)(139).…”