{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:19Z","timestamp":1792785859330,"version":"4.5.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"British Heart Intermediate Basic Science Research Fellowship","award":["FS\/18\/2\/33221"],"award-info":[{"award-number":["FS\/18\/2\/33221"]}],"id":[{"id":"https:\/\/ror.org\/00r0jqe29","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Polycystin-1 (PKD1) and -2 (PKD2) are causative genes for autosomal dominant polycystic kidney disease, which often presents with cardiovascular manifestations by mechanisms still not completely understood. PKD1 and PKD2 have been suggested to function as mechanoreceptors in endothelial cells (ECs), transducing mechanical forces exerted by the flowing blood into downstream signalling pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Our zebrafish functional screening of EC mechanoreceptors identified PKD1 and PKD2 as anti-apoptotic, protective factors in the zebrafish endothelium. In mice, we show that inducible EC-specific loss of PKD1, but not PKD2, led to increased atherosclerosis. To dissect the underlying mechanisms, we performed single cell RNA sequencing and identified candidate pathways regulating EC behaviour downstream from PKD1. Knockdown of PKD1 in human aortic ECs resulted in increased EC apoptosis and decreased expression of athero-protective endothelial nitric oxide synthase, which was mediated by thrombospondin 1 and cellular communication network factor 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>By integrating in vivo and in vitro models with \u2013omics approaches, we have identified PKD1 as a novel regulator of EC survival and protective factor against atherosclerosis development. We conclude that therapeutic targeting of this pathway may treat atherosclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvag171","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:11:48Z","timestamp":1786101108000},"page":"1922-1935","source":"Crossref","is-referenced-by-count":0,"title":["Polycystin-1 suppresses apoptotic signalling in endothelial cells and protects from atherosclerosis"],"prefix":"10.1093","volume":"122","author":[{"given":"Blanca","family":"Tardajos Ayllon","sequence":"first","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]},{"name":"William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Gras Font","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A E","family":"Winks","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4650-9870","authenticated-orcid":false,"given":"Hannah","family":"Grimwood","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Roddie","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ariaans","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Wright","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J A","family":"Chico","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Fragiadaki","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]},{"name":"William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila E","family":"Francis","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert C M","family":"Ong","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C","family":"Evans","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8835-1491","authenticated-orcid":false,"given":"Jovana","family":"Serbanovic-Canic","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield , Sheffield S10 2RX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"2026101011120391000_cvag171-B1","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nrcardio.2015.203","article-title":"Role of biomechanical forces in the natural history of coronary atherosclerosis","volume":"13","author":"Brown","year":"2016","journal-title":"Nat Rev Cardiol"},{"key":"2026101011120391000_cvag171-B2","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1093\/eurheartj\/ehu353","article-title":"Biomechanical factors in atherosclerosis: mechanisms and clinical 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