Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10637/14444
Registro completo de metadatos
Campo DC Valor Lengua/Idioma
dc.contributor.otherUCH. Departamento de Medicina y Cirugía-
dc.contributor.otherProducción Científica UCH 2022-
dc.creatorYeh, Chih-Fan-
dc.creatorCheng, Shih-Hsin-
dc.creatorLin, Yu-Shan-
dc.creatorShentu, Tzu-Pin-
dc.creatorHuang, Ru-Ting-
dc.creatorZhu, Jiayu-
dc.creatorGarcía Fernández, Francisca-
dc.date2022-
dc.date.accessioned2023-06-16T04:00:32Z-
dc.date.available2023-06-16T04:00:32Z-
dc.date.issued2022-01-21-
dc.identifier.citationYeh, C. F., Cheng, S. H., Lin, Y. S., Shentu, T. P., Huang, R. T., Zhu, J., Chen, Y. T., Kumar, S., Lin, M. S., Kao, H. L., Huang, P. H., Roselló-Sastre, E., Garcia, F., Jo, H., Fang, Y. & Yang, K. C. (2022). Targeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo. Science Advances, vol. 8, i. 3 (21 jan.), art. eabl8096. DOI: https://doi.org/10.1126/sciadv.abl8096-
dc.identifier.issn2375-2548 (Electrónico)-
dc.identifier.urihttp://hdl.handle.net/10637/14444-
dc.descriptionEsta comunicación se encuentra disponible en la siguiente URL: https://www.science.org/doi/epdf/10.1126/sciadv.abl8096-
dc.descriptionEn este artículo de investigación también participan: Yen-Ting Chen, Sandeep Kumar, Mao-Shin Lin, Hsien-Li Kao, Po-Hsun Huang, Esther Roselló-Sastre, Hanjoong Jo, Yun Fang y Kai-Chien Yang.-
dc.description.abstractAlthough atherosclerosis preferentially develops at arterial curvatures and bifurcations where disturbed flow (DF) activates endothelium, therapies targeting flow-dependent mechanosensing pathways in the vasculature are unavailable. Here, we provided experimental evidence demonstrating a previously unidentified causal role of DF-induced endothelial TXNDC5 (thioredoxin domain containing 5) in atherosclerosis. TXNDC5 was increased in human and mouse atherosclerotic lesions and induced in endothelium subjected to DF. Endothelium-specific Txndc5 deletion markedly reduced atherosclerosis in ApoE−/− mice. Mechanistically, DF-induced TXNDC5 increases proteasome-mediated degradation of heat shock factor 1, leading to reduced heat shock protein 90 and accelerated eNOS (endothelial nitric oxide synthase) protein degradation. Moreover, nanoparticles formulated to deliver Txndc5-targeting CRISPR-Cas9 plasmids driven by an endothelium-specific promoter (CDH5) significantly increase eNOS protein and reduce atherosclerosis in ApoE−/− mice. These results delineate a new molecular paradigm that DF-induced endothelial TXNDC5 promotes atherosclerosis and establish a proof of concept of targeting endothelial mechanosensitive pathways in vivo against atherosclerosis.-
dc.formatapplication/pdf-
dc.languagees-
dc.language.isoen-
dc.publisherAmerican Association for the Advancement of Science-
dc.relationEste artículo de investigación ha sido financiado por becas del Taiwan Ministry of Science Technology (108-2314-B-002-199-MY3 y 109-2628-B-002-032), del Taiwan National Health Research Institute (NHRI-EX109-10936SI), del CRC Translational Research (IBMS-CRC108-P03), del Institute of Biomedical Sciences at Academia Sinica, Taiwan (AS-TM-109-01-04), del National Taiwan University Hospital (NTUH.107-T02, UN107-019, 107-N4062, VN107-03, 108-T16, VN108-06, VN109-07, VN110-01, NTUH.108-P04, 108-N4198, 108-S4247, 108-EDN03, 109-EDN05, 109-S4576, 110-S4836 y 110-T16), del National Taiwan University College of Medicine and National Taiwan University Hospital (NSCCMOH-131-41, 109C101-41 y 110C101-071), de la National Taiwan University (109L7872), así como del Chicago Biomedical Consortium (A-014), de la American Heart Association (20TPA35490401) y del National Institutes of Health (NIH R01HL138223, R01HL136765, R01HL119798 y R01HL139757).-
dc.relation.ispartofScience Advances, vol. 8, i. 3 (21 jan. 2022)-
dc.rightshttp://creativecommons.org/licenses/by/4.0/deed.es-
dc.subjectAtherosclerosis.-
dc.subjectAteroesclerosis.-
dc.subjectMolecular biology.-
dc.subjectProteínas.-
dc.subjectProteins.-
dc.subjectBiología molecular.-
dc.titleTargeting mechanosensitive endothelial TXNDC5 to stabilize eNOS and reduce atherosclerosis in vivo-
dc.typeArtículo-
dc.identifier.doihttps://doi.org/10.1126/sciadv.abl8096-
dc.centroUniversidad Cardenal Herrera-CEU-
Aparece en las colecciones: Dpto. Medicina y Cirugía




Los ítems de DSpace están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.