Abstract
Simple SummaryMounting evidence suggests a role for extracellular vesicles in cell-to-cell communication, in both physiological and pathological conditions. Moreover, the molecular content of vesicles can be exploited for diagnostic and therapeutic purposes. Inflamed tissues and tumors are often characterized by hypoxic areas, where oxygen levels drop dramatically. Several studies demonstrated that hypoxic stress affects the release of vesicles and their content. This review is intended to provide an exhaustive overview on the relationship between hypoxia and vesicles in inflammatory diseases and cancer.Hypoxia is a severe stress condition often observed in cancer and chronically inflamed cells and tissues. Extracellular vesicles play pivotal roles in these pathological processes and carry biomolecules that can be detected in many biofluids and may be exploited for diagnostic purposes. Several studies report the effects of hypoxia on extracellular vesicles’ release, molecular content, and biological functions in disease. This review summarizes the most recent findings in this field, highlighting the areas that warrant further investigation.
Highlights
Hypoxia as pathological stress arises when blood supply to a tissue is compromised, as in myocardial infarction, renal ischemic injury, or when a reduction of oxygen levels and nutrients occurs in the cellular microenvironment, as in inflammation and solid cancers
Three types of hypoxia-inducible factors (HIFs) are known: HIF1, HIF2, and HIF3. They consist of heterodimers of two subunits, α (HIF1α, HIF2α or HIF3α) and β, while the β subunits are constitutively expressed in the nucleus and are largely insensitive to changes in oxygen tension, the level of the α subunits is acutely oxygen sensitive and they are synthesized de novo at a high rate [61]
We summarize the current literature on the following topics: (a) the effect of hypoxia on the release of vesicles in terms of amount and content; (b) the biological roles of extracellular vesicles released under hypoxia in different types of disease; and (c) the role of HIF signaling pathways in modulating EV release and functions
Summary
In the last two decades, extracellular vesicles (EVs) have been the subject of extensive research. EVs were first discovered in the 1970s and, by this generic term, researchers referred to a heterogeneous group of membrane vesicles with different sizes (from 10 nm to 10 μm), biological origins, and molecular content [1,2,3,4]. The socalled MVs are generated following rearrangement of the cell cytoskeleton and budding of plasma membrane. Instead, are produced after the inward budding of the endosomal membrane and the formation of multivesicular bodies (MVBs). These MVBs can fuse with the cell plasma membrane releasing their content, the exosomes, in the extracellular environment [2,3,5,9]. Plasma and serum accessible, abundant and biobanked Sample representative of the patient status Minimally invasive sampling
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