Abstract
Endothelium has a rich vesicular network that allows the exchange of macromolecules between blood and parenchymal cells. This feature of endothelial cells, along with their polarized secretory machinery, makes them the second major contributor, after platelets, to the particulate secretome in circulation. Extracellular vesicles (EVs) produced by the endothelial cells mirror the remarkable molecular heterogeneity of their parent cells. Cargo molecules carried by EVs were shown to contribute to the physiological functions of endothelium and may support the plasticity and adaptation of endothelial cells in a paracrine manner. Endothelium-derived vesicles can also contribute to the pathogenesis of cardiovascular disease or can serve as prognostic or diagnostic biomarkers. Finally, endothelium-derived EVs can be used as therapeutic tools to target endothelium for drug delivery or target stromal cells via the endothelial cells. In this review we revisit the recent evidence on the heterogeneity and plasticity of endothelial cells and their EVs. We discuss the role of endothelial EVs in the maintenance of vascular homeostasis along with their contributions to endothelial adaptation and dysfunction. Finally, we evaluate the potential of endothelial EVs as disease biomarkers and their leverage as therapeutic tools.
Highlights
Endothelium is a key gateway for communication between blood and stroma
In this review we revisited the extraordinary molecular and functional diversity of the vascular endothelium, which supports the notion that endothelial cells are programmed to serve specific functional adaptations of the vascular bed where they belong, which, in turn, is fine-tuned to the physiologic requirements of the adjacent stroma
We emphasized the physiological heterogeneity of endothelial cells along with their maladaptive plasticity in disease
Summary
Endothelium is a key gateway for communication between blood and stroma. Recent evidence highlights the remarkable heterogeneity and plasticity of the endothelial cells in development, health and disease. The particulate secretomes of endothelia mirror their molecular heterogeneity and may support plasticity and adaptation of endothelial cells within or between different vascular beds while having significant functional impacts on circulating cells, including immune cells in blood or lymph. Cellular plasticity is the biological phenomenon whereby a terminally differentiated cell may take on a new specialized identity This process can occur in response to physiological or pathological environmental cues and involves repression and activation of genes associated with the new cellular functions. Endothelial cells (ECs) are highly plastic, able to modulate their phenotype and function in response to stimuli in a variety of developmental, physiological and pathological processes This plasticity in response to physiological cues and in disease results in a remarkable phenotypic heterogeneity. ECs arise from the mesoderm during embryonic development; they initially exhibit a non-specialized phenotype and develop specialized identities specific to their vascular beds
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