Human Aortic Stenotic Valve-Derived Extracellular Vesicles Induce Endothelial Dysfunction

and Thrombogenicity Through AT1R/NADPH Oxidases/SGLT2 Pro-Oxidant Pathway.

Volume 9, Issue 7, July 2024, Pages 845-864.

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Significance :

Thrombogenic Potential of AS Valves:Human calcified aortic stenosis (AS) valves are a

significant reservoir of thrombotic material, including procoagulant extracellular vesicles (EVs),

tissue factor (TF), and PAI-1.These EVs and other procoagulant substances transform the

endothelial cells of the valve into a prothrombotic, proadhesive, and proinflammatory surface,

which promotes thrombogenesis and recruits inflammatory cells.This suggests that calcified

AS valves may significantly contribute to thrombosis, increasing the risk of complications like

stroke, and provides insights into potential therapeutic targets to reduce thrombotic risk in AS patients.

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Importance of lipidology :

Although the provided text doesn't specifically focus on lipids, the inflammatory and oxidative

stress pathways in AS directly relate to lipid metabolism. The upregulation of ACE, SGLT2,

and oxidative stress markers in the calcified portion of AS valves could influence lipid handling,

as oxidative stress and inflammation often affect lipid profiles in cardiovascular diseases.

Exploring the role of lipids in the formation of EVs and their contribution to endothelial dysfunction

could enhance understanding of how lipid-related factors influence valve calcification, thrombosis,

and overall disease progression.

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Connectivity to other fields :

The involvement of oxidative stress in endothelial dysfunction and valve calcification connects the

study to redox biology. The finding that SGLT2 upregulation in VECs is mediated by NADPH

oxidases in a redox-sensitive manner opens up potential areas for research in redox biology,

particularly in cardiovascular diseases.

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https://doi.org/10.1016/j.jacbts.2024.02.012