Skip to main content

Research Repository

Advanced Search

?-catenin promotes endothelial survival by regulating eNOS activity and flow-dependent anti-apoptotic gene expression

Tajadura, V; Hansen, M H; Smith, J; Charles, H; Rickman, M; Farrell-Dillon, K; Claro, V; Warboys, C; Ferro, A


V Tajadura

M H Hansen

J Smith

H Charles

M Rickman

K Farrell-Dillon

V Claro

C Warboys

A Ferro


Increased endothelial cell (EC) apoptosis is associated with the development of atherosclerotic plaques that develop predominantly at sites exposed to disturbed ?ow (DF). Strategies to promote EC survival may therefore represent a novel therapeutic approach in cardiovascular disease. Nitric oxide (NO) and ?-catenin have both been shown to promote cell survival and they interact in ECs as we previously demonstrated. Here we investigated the physiological role of ?-catenin as a mediator of NO-induced cell survival in ECs. We found that ?-catenin depleted human umbilical vein ECs (HUVEC) stimulated with pharmacological activators of endothelial NO synthase (eNOS) showed a reduction in eNOS phosphorylation (Ser1177) as well as reduced intracellular cyclic guanosine monophosphate levels compared to control cells in static cultures. In addition, ?-catenin depletion abrogated the protective effects of the NO donor, Snitroso-N-acetylpenicillamine, during TNF?- and H2O2-induced apoptosis. Using an orbital shaker to generate shear stress, we con?rmed eNOS and ?-catenin interaction in HUVEC exposed to undisturbed ?ow and DF and showed that ?-catenin depletion reduced eNOS phosphorylation. ?-catenin depletion promoted apoptosis exclusively in HUVEC exposed to DF as did inhibition of soluble guanylate cyclase (sGC) or ?-catenin transcriptional activity. The expression of the pro-survival genes, Bcl-2 and survivin was also reduced following inhibition of ?-catenin transcriptional activity, as was the expression of eNOS. In conclusion, our data demonstrate that ?-catenin is a positive regulator of eNOS activity and cell survival in human ECs. sGC activity and ?-catenin-dependent transcription of Bcl-2, survivin, BIRC3 and eNOS are essential to maintain cell survival in ECs under DF.


Tajadura, V., Hansen, M. H., Smith, J., Charles, H., Rickman, M., Farrell-Dillon, K., …Ferro, A. (2020). β-catenin promotes endothelial survival by regulating eNOS activity and flow-dependent anti-apoptotic gene expression. Cell Death and Disease, 11(6),

Journal Article Type Article
Acceptance Date Jun 15, 2020
Publication Date Jun 30, 2020
Deposit Date Aug 6, 2020
Publicly Available Date Nov 20, 2020
Journal Cell Death & Disease
Print ISSN 2041-4889
Publisher Springer Nature [academic journals on]
Peer Reviewed Peer Reviewed
Volume 11
Issue 6
Public URL
Publisher URL


You might also like

Downloadable Citations