Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers (original) (raw)
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Biomolecules, 2021
Extracellular vesicles (EVs) are composed of a lipid bilayer containing transmembrane and soluble proteins. Subtypes of EVs include ectosomes (microparticles/microvesicles), exosomes, and apoptotic bodies that can be released by various tissues into biological fluids. EV cargo can modulate physiological and pathological processes in recipient cells through near- and long-distance intercellular communication. Recent studies have shown that origin, amount, and internal cargos (nucleic acids, proteins, and lipids) of EVs are variable under different pathological conditions, including cardiovascular diseases (CVD). The early detection and management of CVD reduce premature morbidity and mortality. Circulating EVs have attracted great interest as a potential biomarker for diagnostics and follow-up of CVD. This review highlights the role of circulating EVs as biomarkers for diagnosis, prognosis, and therapeutic follow-up of CVD, and also for drug delivery. Despite the great potential of E...
Extracellular Vesicles in Immunology
Extracellular Vesicles in Health and Disease, 2014
Cardiovascular diseases (CVD) represent the leading cause of morbidity and mortality globally. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for diagnosis, prognosis, and therapy in CVD. The ubiquitous nature of EVs in biological fluids presents a technological advantage compared to current diagnostic tools by virtue of their notable stability. EV contents, such as proteins and microRNAs, represent specific signatures of cellular activation or injury. This feature positions EVs as an alternative source of biomarkers. Furthermore, their intrinsic activity and immunomodulatory properties offer EVs unique opportunities to act as therapeutic agents per se or to serve as drug delivery carriers by acting as miniaturized vehicles incorporating bioactive molecules. In this article, we aim to review the recent advances and applications of EV-based biomarkers and therapeutics. In addition, the potential of EVs as a drug delivery and theranostic platform for CVD will also be discussed.
Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases
Frontiers in Immunology, 2014
Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are small vesicles secreted from a wide variety of cells. Whereas MVs are particles released by the outward budding of the plasma membrane, exosomes are derived from endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and increased plasma circulating levels of EVs have been correlated with pathophysiological situations. MVs, already present in the blood of healthy individuals, are considerably elevated in several cardiovascular diseases associated with inflammation, suggesting that they can mediate deleterious effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent studies also demonstrate that MVs may act as biological information vectors transferring proteins or genetic material to maintain cell homeostasis, favor cell repair, or even promote angiogenesis. Additionally, exosomes have also been shown to have pro-angiogenic and cardio-protective properties. These beneficial effects, therefore, reveal the potential therapeutical use of EVs in the field of cardiovascular medicine and regenerative therapy. In this review, we will provide an update of cellular processes modulated by EVs of specific interest in the treatment of cardiovascular pathologies. A special focus will be made on the morphogen sonic hedgehog (Shh) associated with EVs (EVs Shh+), which have been shown to mediate many pro-angiogenic effects. In addition to offer a potential source of cardiovascular markers, therapeutical potential of EVs reveal exciting opportunities to deliver specific agents by non-immunogenic means to cardiovascular system.
Frontiers in Cell and Developmental Biology, 2022
Cardiovascular diseases (CVDs) are the first cause of death worldwide. In recent years, there has been great interest in the analysis of extracellular vesicles (EVs), including exosomes and microparticles, as potential mediators of biological communication between circulating cells/plasma and cells of the vasculature. Besides their activity as biological effectors, EVs have been also investigated as circulating/systemic biomarkers in different acute and chronic CVDs. In this review, the role of EVs as potential diagnostic and prognostic biomarkers in chronic cardiovascular diseases, including atherosclerosis (mainly, peripheral arterial disease, PAD), aortic stenosis (AS) and aortic aneurysms (AAs), will be described. Mechanistically, we will analyze the implication of EVs in pathological processes associated to cardiovascular remodeling, with special emphasis in their role in vascular and valvular calcification. Specifically, we will focus on the participation of EVs in calcium accumulation in the pathological vascular wall and aortic valves, involving the phenotypic change of vascular smooth muscle cells (SMCs) or valvular interstitial cells (IC) to osteoblast-like cells. The knowledge of the implication of EVs in the pathogenic mechanisms of cardiovascular remodeling is still to be completely deciphered but there are promising results supporting their potential translational application to the diagnosis and therapy of different CVDs.
Extracellular vesicles: new players in cardiovascular diseases
The international journal of biochemistry & cell biology, 2014
a b s t r a c t Extracellular vesicles, particles released by all cell types, represent a new way to convey information between cells such as proteins, second messengers, and genetic information to modify the phenotype and function of the target cells. Recent data suggest that extracellular vesicles play a crucial role in both physiology and pathology, including coagulation, angiogenesis, cell survival, modulation of the immune response, and inflammation. Thus extracellular vesicles participate in the processes of cardiovascular diseases from atherosclerosis, myocardial infarction to heart failure. Consequently, extracellular vesicles can potentially be exploited for therapy, prognosis, and biomarkers for health and disease. This review focuses on the role of extracellular vesicles in the development of cardiovascular diseases, as well as the deleterious and beneficial effects that they may provide in vascular cells and myocardium.
Extracellular vesicles characteristics and emerging roles in atherosclerotic cardiovascular disease
Metabolism-clinical and Experimental, 2018
The term extracellular vesicles (EVs) describes membrane vesicles released into the extracellular space by most cell types. EVs have been recognized to play an important role in cell-to-cell communication. They are known to contain various bioactive molecules, including proteins, lipids, and nucleic acids. Although the nomenclature of EVs is not entirely standardized, they are considered to include exosomes, microparticles or microvesicles and apoptotic bodies. EVs are believed to play important roles in a wide range of biological processes. Although the pathogenic roles of EVs are largely documented, their protective roles are not as well established. Cardiovascular disease represents one of the most relevant and rapidly growing areas of the EV research. Circulating EVs released from platelets, erythrocytes, leukocytes, and endothelial cells may contain potentially valuable biological information for biomarker development in cardiovascular disease and could serve as a vehicle for therapeutic use. Herein, we provide an overview of the current knowledge in EV in cardiovascular disease, including a discussion on challenges in EV research, EV properties in various cell types, and their importance in atherosclerotic disease.
Cardiovascular Research, 2022
Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are released from cells of the cardiovascular system, and are considered important mediators of intercellular and extracellular communications. Two types of EVs of particular interest are exosomes and microvesicles, which have been identified in all tissue and body fluids and carry a variety of molecules including RNAs, proteins, and lipids. EVs have potential for use in the diagnosis and prognosis of cardiovascular diseases and as new therapeutic agents, particularly in the setting of myocardial infarction and heart failure. Despite their promise, technical challenges related to their small size make it challenging to accurately identify and characterize them, and to study EV-mediated processes. Here, we aim to provide the reader with an overview of the techniques and technologies available for the separation and characterization of EVs from different sources. Methods for determining the protein, RNA, and...
Molecular & Cellular Proteomics, 2016
Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected postinfarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p ؍ 0.012; Complement C5 (C5), 1.27-fold change, p ؍ 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p ؍ 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p ؍ 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p ؍ 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p ؍ 0.005); C5 (p ؍ 0.0047), APOD (p ؍ 0.0267); APOC3 (p ؍ 0.0064); GP1BA (p ؍ 0.0031); PPBP (p ؍ 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases (CADs).
International Journal of Molecular Sciences
Cells convey information among one another. One instrument employed to transmit data and constituents to specific (target) cells is extracellular vesicles (EVs). They originate from a variety of cells (endothelial, immune cells, platelets, mesenchymal stromal cells, etc.), and consequently, their surface characteristics and cargo vary according to the paternal cell. The cargo could be DNA, mRNA, microRNA, receptors, metabolites, cytoplasmic proteins, or pathological molecules, as a function of which EVs exert different effects upon endocytosis in recipient cells. Recently, EVs have become important participants in a variety of pathologies, including atherogenesis and coronavirus disease 2019 (COVID-19)-associated thrombosis. Herein, we summarize recent advances and some of our own results on the role of EVs in atherosclerotic cardiovascular diseases, and discuss their potential to function as signaling mediators, biomarkers and therapeutic agents. Since COVID-19 patients have a high...