Extracellular vesicles in vascular pathophysiology: beyond their molecular content

Abstract

Extracellular vesicles in vascular pathophysiology 1 Currently, the topic of extracellular vesicles (EVs) and their involvement in disease promotion and progression is gaining important insight in diagnostics and treatment. 5 In this review, we focus on specific EV characteristics, still not intensively investigated, which contribute to the biological activity of EVs, that is, composition of the EV surface called a corona, and its charge.The biological activity of EVs depends on their cargo and their biological availability and biostability. The estimated blood plasma concentration of EVs in healthy individuals is between 10 8 and 10 14 EVs/ml. Such discrepancies, more than 6 orders of magnitude, depend mainly on the isolation protocol and possible contamination by other colloidal particles present in the plasma, such as lipoproteins and large protein aggregates. 6 In total platelet poor plasma, the average platelet microvesicle (PMV) content has been estimated at 10 9 to 10 10 EVs/ml in patients on antiplatelet drugs and healthy individuals. PMV abundance depends mainly on the plasma purity and preanalytical handling. 7-11 Assuming that one -third of the plasma EVs is of platelet origin, the number of the plasma EVs can be approximately 10 10 EVs/ml. 6 The average plasma residence time of intravenously delivered EVs ranges from 30 to 80 minutes and it is mainly regulated by the phagocyting activity of the mononuclear phagocyte system and by Introduction When about 50 years ago Wolf 1 noticed that some tiny and highly abundant objects present in human blood plasma contribute to clotting events, it seemed that there is something beyond clotting factors that may support platelets / thrombocytes in their aggregation and formation of a thrombus. This coagulant particulate material released from platelets (referred to as "platelet dust") was produced in considerably larger amounts than required for thrombin generation. It was detected not only in plasma but also in serum, and its presence seemed to be associated with the platelet -like activity of the serum. 1 The platelet activation leads to secretion of granules containing the procoagulant material and proteins involved in cytoskeletal arrangement, synaptic transportation, and secretion from their internal space. 2 The processes of the formation and secretion of platelet "particles" are analogous to the processes occurring in other cells, including endothelial cells. They result in the formation of 2 types of membrane vesicles: bigger ones shed from the surface and named microvesicles (ectosomes) of 100 nm to 1 µm in diameter, and exosomes, measuring 40 nm to 100 nm in diameter. The latter are similar in size to the internal vesicles in multivesicular bodies (MVBs) and α -granules, 3,4 and can be compared to endothelial vesiculation (FIguRE 1).

Proteomic Profiling of Extracellular Vesicles Isolated from Plasma and Peritoneal Exudate in Mice Induced by Crotalus scutulatus scutulatus Crude Venom and Its Purified Cysteine-Rich Secretory Protein (Css-CRiSP)

“…Proteomic analysis is a well-established approach for identifying EV proteins involved in the development and progression of various diseases, including neurodegenerative diseases, cancers, injury, local and systemic inflammation, and vascular pathophysiology [39][40][41][42][43][44][45][46][47][48]. Identification of EV protein candidates can help discover novel EV-based This comparison revealed a consistency in the over-expression and suppression of similar proteins in both treatments (vEV and CRiSP-EV) in exudate and plasma, indicating that Css-CRiSP could potentially be involved in the immediate effects of the envenomation.…”

“…Proteomic analysis is a well-established approach for identifying EV proteins involved in the development and progression of various diseases, including neurodegenerative diseases, cancers, injury, local and systemic inflammation, and vascular pathophysiology [39][40][41][42][43][44][45][46][47][48]. Identification of EV protein candidates can help discover novel EV-based biomarkers for diagnosis, prognosis, and monitoring of disease progression.…”

Revealing sphingolipids composition in extracellular vesicles and paternal β-cells after persistent hyperglycemia

“…The intensity values for the mentioned mass also differed in the case of large and small EVs, for which HG caused an increase in the content of this CER. In the case of large EVs, differences were also demonstrated for [C 41 H 77 NO 3 ] + -Cer 41:3, the content of which decreased with the increased glucose level, and for [C 42 H 81NO 3 ]…”

“…Sphingolipids (SPs), including ceramides (CERs), hexosylceramides (HexCERs) and glycosphingolipids (GSLs), represent a ubiquitous and structurally miscellaneous class of lipids involved in physiological and pathological processes, possessing both signaling and structural properties [1,2]. Lipid membrane composition is varied in different cell compartments, and having impact on such cell membrane properties, charge and protein corona [3]. Hyperglycemia (HG) is an example of a physiological condition initiated by the elevated blood glucose levels, which, when out of control of the sensitive fuse that is the hormone insulin), causes metabolic stress, which, if it continues chronically, can cause pathological conditions.…”

Spectroscopic insight into breast cancer: profiling small extracellular vesicles lipids via infrared spectroscopy for diagnostic precision

“…In this review, we delve into specific characteristics of sEVs that remain relatively unexplored but contribute significantly to their biological activity. Let’s explore the fascinating world of EVs beyond their molecular content 6 , 7 .…”