Extracellular vesicles in cardiovascular disease: Biological functions and therapeutic implications.

Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer particles naturally released from the cell. While exosomes are formed as intraluminal vesicles (ILVs) of the multivesicular endosomes (MVEs) and released to extracellular space upon MVE-plasma membrane fusion, microvesicles are generated through direct outward budding of the plasma membrane. Exosomes and microvesicles have same membrane orientation, different yet overlapping sizes; their cargo contents are selectively packed and dependent on the source cell type and functional state. Both exosomes and microvesicles can transfer bioactive RNAs, proteins, lipids, and metabolites from donor to recipient cells and influence the biological properties of the latter. Over the last decade, their potential roles as effective inter-tissue communicators in cardiovascular physiology and pathology have been increasingly appreciated. In addition, EVs are attractive sources of biomarkers for the diagnosis and prognosis of diseases, because they acquire their complex cargoes through cellular processes intimately linked to disease pathogenesis. Furthermore, EVs obtained from various stem/progenitor cell populations have been tested as cell-free therapy in various preclinical models of cardiovascular diseases and demonstrate unequivocally encouraging benefits. Here we summarize the findings from recent research on the biological functions of EVs in the ischemic heart disease and heart failure, and their potential as novel diagnostic biomarkers and therapeutic opportunities.

Han C ，Yang J ，Sun J ，Qin G ... -  《-》

Extracellular Vesicles in Cardiovascular Pathophysiology: Communications, Biomarkers, and Therapeutic Potential.

Extracellular vesicles (EVs) are diverse, membrane-bound vesicles released from cells into the extracellular environment. They originate from either endosomes or the cell membrane and typically include exosomes and microvesicles. These EVs serve as crucial mediators of intercellular communication, carrying a variety of contents such as nucleic acids, proteins, and lipids, which regulate the physiological and pathological processes of target cells. Moreover, the molecular cargo of EVs can reflect critical information about the originating cells, making them potential biomarkers for the diagnosis and prognosis of diseases. Over the past decade, the role of EVs as key communicators between cell types in cardiovascular physiology and pathology has gained increasing recognition. EVs from different cellular sources, or from the same source under different cellular conditions, can have distinct impacts on the management, diagnosis, and prognosis of cardiovascular diseases. Furthermore, it is essential to consider the influence of cardiovascular-derived EVs on the metabolism of peripheral organs. This review aims to summarize recent advancements in the field of cardiovascular research with respect to the roles and implications of EVs. Our goal is to provide new insights and directions for the early prevention and treatment of cardiovascular diseases, with an emphasis on the therapeutic potential and diagnostic value of EVs.

Cui Z ，Zhang L ，Hu G ，Zhang F ... -  《-》

Circulating Extracellular Vesicles As Biomarkers and Drug Delivery Vehicles in Cardiovascular Diseases.

de Freitas RCC ，Hirata RDC ，Hirata MH ，Aikawa E ... -  《Biomolecules》

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases.

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.

Rezaie J ，Rahbarghazi R ，Pezeshki M ，Mazhar M ，Yekani F ，Khaksar M ，Shokrollahi E ，Amini H ，Hashemzadeh S ，Sokullu SE ，Tokac M ... -  《-》

Metabolites as extracellular vesicle cargo in health, cancer, pleural effusion, and cardiovascular diseases: An emerging field of study to diagnostic and therapeutic purposes.

Extracellular vesicles (EVs) are highly diverse nanoscale membrane-bound structures released from different cell types into the extracellular environment. They play essential functions in cell signaling by transporting their cargo, such as proteins, RNA, DNA, lipids, metabolites, and small molecules, to recipient cells. It has recently been shown that EVs might modulate carcinogenesis by delivering cargo to recipient cells. Furthermore, recent discoveries revealed that changes in plasma-derived EV levels and cargo in subjects with metabolic diseases were documented by many researchers, suggesting that EVs might be a promising source of disease biomarkers. One of the cargos of EVs that has recently attracted the most attention is metabolites. The metabolome of these vesicles introduces a plethora of disease indicators; hence, examining the metabolomics of EVs detected in human biofluids would be an effective approach. On the other hand, metabolites have various roles in biological systems, including the production of energies, synthesizing macromolecules, and serving as signaling molecules and hormones. Metabolome rewiring in cancer and stromal cells is a characteristic of malignancy, but the current understanding of how this affects the metabolite composition and activity of tumor-derived EVs remains in its infancy. Since new findings and studies in the field of exosome biology and metabolism are constantly being published, it is likely that diagnostic and treatment techniques, including the use of exosome metabolites, will be launched in the coming years. Recent years have seen increased interest in the EV metabolome as a possible source for biomarker development. However, our understanding of the role of these molecules in health and disease is still immature. In this work, we have provided the latest findings regarding the role of metabolites as EV cargoes in the pathophysiology of diseases, including cancer, pleural effusion (PE), and cardiovascular disease (CVD). We also discussed the significance of metabolites as EV cargoes of microbiota and their role in host-microbe interaction. In addition, the latest findings on metabolites in the form of EV cargoes as biomarkers for disease diagnosis and treatment are presented in this study.

Zhang Y ，Liang F ，Zhang D ，Qi S ，Liu Y ... -  《-》