Oscillatory shear stress induced extracellular vesicles mediate valvular endothelial-interstitial cell crosstalk exacerbating aortic valve calcification

Here, we identify a novel extracellular vesicle-derived circRNA, CircILRUN, originating from hVECs and demonstrate its critical function in promoting hVIC osteogenesis and CAVD progression in vitro and in vivo.

CircILRUN expression is significantly elevated in extracellular vesicles from hVECs under oscillatory shear stress. Its deletion markedly attenuates aortic valve calcification (AVC) in mice, reducing valve thickness, calcium deposition, and improving echocardiographic parameters, findings corroborated in osteogenic medium-induced hVICs. Through unbiased protein-RNA screening and biochemical validation, we identify N-acetyltransferase 10 (NAT10) as a key target of CircILRUN.