Nitrite-derived nitric oxide reduces hypoxia-inducible factor 1α-mediated extracellular vesicle production by endothelial cells

<p> Extracellular vesicles (EVs) are small, spherical particles enclosed by a <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/phospholipid-bilayer" target="_blank">phospholipid bilayer</a> (∼30–1000 nm) released from multiple cell types, and have been shown to have pathophysiological roles in a plethora of disease states. The transcription factor hypoxia-inducible factor-1 (HIF-1) allows for adaptation of cellular physiology in hypoxia and may permit the enhanced release of EVs under such conditions. <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/nitric-oxide" target="_blank">Nitric oxide</a> (NO) plays a pivotal role in vascular <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/homeostasis" target="_blank">homeostasis</a>, and can modulate the cellular response to hypoxia by preventing HIF-1 accumulation. We aimed to selectively target HIF-1 via sodium nitrite (NaNO2) addition, and examine the effect on endothelial EV, size, concentration and function, and delineate the role of HIF-1 in EV biogenesis. </p>