Extracellular Vesicles as Drivers of Immunoinflammation in Atherothrombosis

Abstract

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality all over the world. Extracellular vesicles (EVs), small lipid-bilayer membrane vesicles released by most cellular types, exert pivotal and multifaceted roles in physiology and disease. Emerging evidence emphasizes the importance of EVs in intercellular communication processes with key effects on cell survival, endothelial homeostasis, inflammation, neoangiogenesis, and thrombosis. This review focuses on EVs as effective signaling molecules able to both derail vascular homeostasis and induce vascular dysfunction, inflammation, plaque progression, and thrombus formation as well as drive anti-inflammation, vascular repair, and atheroprotection. We provide a comprehensive and updated summary of the role of EVs in the development or regression of atherosclerotic lesions, highlighting the link between thrombosis and inflammation. Importantly, we also critically describe their potential clinical use as disease biomarkers or therapeutic agents in atherothrombosis.

Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

“…The discovery of vesicular transport machinery that governs vesicle trafficking from one cell and transfers cargos and elicits signaling in a recipient cell was so groundbreaking that it earned James Rothman, Randy Schekman, and Thomas Südhof the 2013 Nobel Prize in Physiology or Medicine [ 3 ]. EVs have been investigated to understand cell-to-cell communication and phenomena within the cellular microenvironment in various fields, including cancer biology [ 4 , 5 ], cardiology [ 6 ], coagulation [ 7 , 8 ], immunology [ 9 ], immunometabolism [ 10 ], neurology [ 11 ], and stem cell biology [ 12 ]. EVs released from specific cells have been studied for therapeutic purposes, including mesenchymal stem cell-derived EVs for regenerative medicine [ 13 ] and SARS-CoV-2 infection [ 14 ], and red blood cell-derived EVs for a drug delivery system [ 15 ].…”

Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets

“…3,4 Compelling evidence shows that EVs associate with several major risk factors and | 7 participate in the development and progression of atherothrombotic disease. 1,5 While considerable challenges remain in terms of detection technologies and clinical translation, EVs are at the forefront of cardiovascular research. 6 Atherosclerotic cardiovascular disease (ASCVD) is a global health problem and the major cause of major adverse cardiac events and cardiovascular mortality.…”

“…The understanding of extracellular vesicles (EVs) has massively evolved over the last decades. EVs are nano‐sized lipid bilayer particles released by all prokaryotic and eukaryotic cells and tissues into interstitial compartments and body intracellular fluids 1 . Interestingly, EVs are professional messengers fully equipped with molecular cargoes (proteins, lipids, and nucleic acids) that contribute to cell‐to‐cell communication either locally or at long distance via the bloodstream 2 .…”

“…Their unique features confer them multiple biological effects both in health and disease 3,4 . Compelling evidence shows that EVs associate with several major risk factors and participate in the development and progression of atherothrombotic disease 1,5 . While considerable challenges remain in terms of detection technologies and clinical translation, EVs are at the forefront of cardiovascular research 6 …”

Regulation of Extracellular Vesicle-Mediated Immune Responses against Antigen-Specific Presentation

“…Extracellular vesicles (EVs) are lipid bilayer structures secreted by living cells and are classified into either exosomes, microvesicles (MVs), or apoptotic bodies, based on the intracellular production mechanism and size ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , …”