Human Aortic Stenotic Valve-Derived Extracellular Vesicles Induce Endothelial Dysfunction and Thrombogenicity Through AT1R/NADPH Oxidases/SGLT2 Pro-Oxidant Pathway

Sandy Hmadeh; Antonin Trimaille; Kensuke Matsushita; Benjamin Marchandot; Adrien Carmona; Fatiha Zobairi; Chisato Sato; Michel Kindo; Tam Minh Hoang; Florence Toti; Kazem Zibara; Eva Hamade; Valérie Schini-Kerth; Gilles Kauffenstein; Olivier Morel

doi:10.1016/j.jacbts.2024.02.012

Human Aortic Stenotic Valve-Derived Extracellular Vesicles Induce Endothelial Dysfunction and Thrombogenicity Through AT1R/NADPH Oxidases/SGLT2 Pro-Oxidant Pathway

JACC Basic Transl Sci. 2024 May 29;9(7):845-864. doi: 10.1016/j.jacbts.2024.02.012. eCollection 2024 Jul.

Authors

Sandy Hmadeh¹, Antonin Trimaille^{1

2}, Kensuke Matsushita^{1

2}, Benjamin Marchandot², Adrien Carmona², Fatiha Zobairi¹, Chisato Sato^{1

2}, Michel Kindo², Tam Minh Hoang², Florence Toti¹, Kazem Zibara³, Eva Hamade³, Valérie Schini-Kerth¹, Gilles Kauffenstein¹, Olivier Morel^{1

2

4}

Affiliations

¹ UR 3074 Translational Cardiovascular Medicine, CRBS, Strasbourg, France.
² Department of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France.
³ Faculty of Sciences, Laboratory of Genomics and Health, Lebanese University, Hadath, Lebanon.
⁴ Hanoï Medical University, Hanoi, Vietnam.

Abstract

Pathological tissues release a variety of factors, including extracellular vesicles (EVs) shed by activated or apoptotic cells. EVs trapped within the native pathological valves may act as key mediators of valve thrombosis. Human aortic stenosis EVs promote activation of valvular endothelial cells, leading to endothelial dysfunction, and proadhesive and procoagulant responses.

Keywords: SGLT2i; SVD; TAVI; TAVR; aortic stenosis; extracellular vesicles; inflammation; leaflet; microparticles; thrombosis.