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http://purl.uniprot.org/citations/36794585http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36794585http://www.w3.org/2000/01/rdf-schema#comment"

Background

Hemodynamic wall shear stress (WSS) exerted on the endothelium by flowing blood determines the spatial distribution of atherosclerotic lesions. Disturbed flow (DF) with a low WSS magnitude and reversing direction promotes atherosclerosis by regulating endothelial cell (EC) viability and function, whereas un-DF which is unidirectional and of high WSS magnitude is atheroprotective. Here, we study the role of EVA1A (eva-1 homolog A), a lysosome and endoplasmic reticulum-associated protein linked to autophagy and apoptosis, in WSS-regulated EC dysfunction.

Methods

The effect of WSS on EVA1A expression was studied using porcine and mouse aortas and cultured human ECs exposed to flow. EVA1A was silenced in vitro in human ECs and in vivo in zebrafish using siRNA (small interfering RNA) and morpholinos, respectively.

Results

EVA1A was induced by proatherogenic DF at both mRNA and protein levels. EVA1A silencing resulted in decreased EC apoptosis, permeability, and expression of inflammatory markers under DF. Assessment of autophagic flux using the autolysosome inhibitor, bafilomycin coupled to the autophagy markers LC3-II (microtubule-associated protein 1 light chain 3-II) and p62, revealed that EVA1A knockdown promotes autophagy when ECs are exposed to DF, but not un-DF . Blocking autophagic flux led to increased EC apoptosis in EVA1A-knockdown cells exposed to DF, suggesting that autophagy mediates the effects of DF on EC dysfunction. Mechanistically, EVA1A expression was regulated by flow direction via TWIST1 (twist basic helix-loop-helix transcription factor 1). In vivo, knockdown of EVA1A orthologue in zebrafish resulted in reduced EC apoptosis, confirming the proapoptotic role of EVA1A in the endothelium.

Conclusions

We identified EVA1A as a novel flow-sensitive gene that mediates the effects of proatherogenic DF on EC dysfunction by regulating autophagy."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.122.318110"xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Feng S."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Souilhol C."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Evans P.C."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Chico T.J.A."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Serbanovic-Canic J."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Diagbouga M.R."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Pirri D."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Canham L."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Tardajos Ayllon B."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Sendac S."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/author"Wolodimeroff E."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/pages"547-561"xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/title"EVA1A (Eva-1 Homolog A) Promotes Endothelial Apoptosis and Inflammatory Activation Under Disturbed Flow Via Regulation of Autophagy."xsd:string
http://purl.uniprot.org/citations/36794585http://purl.uniprot.org/core/volume"43"xsd:string
http://purl.uniprot.org/citations/36794585http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36794585
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