#DisturbedFlow

Mechano-vulnerability of #EndothelialCell in #Atherosclerosis

EVA1A, elevated by #DisturbedFlow-Twist1 axis, blocks EC #Autophagy & induces #Apoptosis

Dr. Paul Evans & Jovana Serbanovic-Canic lab ATVB 2023
https://www.ahajournals.org/doi/10.1161/ATVBAHA.122.318110

Interesting to note that LC3B in EC +72 h #DisturbedFlow is mostly lipidated (Fig. 4A)

Does this suggest that endothelium under #DisturbedFlow enter an Autophagy-dependent state? For Survival, Shear-sensing & Secretion?

#LaminarShear pushes VE-PTP (How?) to downstream pole of #EndothelialCell, followed by endocytosis->p-Tie2

Potentially explain how #DisturbedFlow#VascularPermeability & #Atherosclerosis

Inhibition of VE-PTP by AKB-9785 fortifies #EndothelialBarrier & reduces Atheromas at atheroprone regions (aortic arch inner curvature, arch+intercostal bifurcations)

Nice comparison of anti-leakage strategies
VE-PTP inhibition
Angpt1 activation of Tie2
Angpt2 inhibition

Dr. Donald McDonald & Dietmar Vestweber labs EMBO Mol Med 2023
https://www.embopress.org/doi/

A remarkable mechanism for #DisturbedFlow disruption of #EndothelialCell Junction in #Atherosclerosis

Disturbed Flow-activated GRK2 phosphorylates #Vinculin Ser721-> a closed conformation of Vinculin
->VE-cad junction

Dr. Jeng-Jiann Chiu lab Euro Heart J 2022
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac647/6830649