Marc A. Augenreich, Larissa Ferreira-Santos, Gavin Power, Francisco I. Ramirez-Perez, Juan D. Gonzalez-Vallejo, M. Williams, Natnicha Imkaew, Min Jeong Cho, Andrew A. Wheeler, Camila Manrique-Acevedo, Luis A. Martinez-Lemus, Jaume Padilla
We provide evidence that neuraminidase, which is elevated in plasma from males and females with type 2 diabetes (T2D), is involved in the activation of endothelial ADAM17 and shedding of the mechanosensor glypican-1. We also provide evidence that neuraminidase-induced ADAM17 activation and consequent glypican-1 shedding are mediated by ANO6 scramblase externalization of phosphatidylserine. Together, this work suggests the neuraminidase-ANO6-ADAM17 axis may be a mechanism underlying impaired endothelial shear stress mechanotransduction in T2D.