{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:01:49Z","timestamp":1777680109519,"version":"3.51.4"},"reference-count":40,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000900","name":"California Institute for Regenerative Medicine","doi-asserted-by":"crossref","award":["CIRM TRAN-12097"],"award-info":[{"award-number":["CIRM TRAN-12097"]}],"id":[{"id":"10.13039\/100000900","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"crossref","award":["PG\/22\/11083"],"award-info":[{"award-number":["PG\/22\/11083"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["104931\/Z\/14\/Z"],"award-info":[{"award-number":["104931\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/L015129\/1"],"award-info":[{"award-number":["BB\/L015129\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Regencor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The epicardium contributes to cardiac development and regeneration, primarily through paracrine signalling. However, the impact of severe hypoxic stress, such as occurs immediately following myocardial infarction, on the activity of the epicardial secretome remains poorly defined. Here we investigated the angiogenic potential of the epicardial secretome under normoxic and hypoxic conditions. In contrast to expectation, the results demonstrate that the angiogenic effect of epicardial cells on vascular endothelium is hampered under severe hypoxia. Mechanistically, we found that hypoxia-mediated sialylation remodels the epicardial secretome altering its angiogenic potential. Severe hypoxia suppresses St6gal1 gene expression decreasing the level of \u03b12,6-sialylation, as measured by comprehensive lectin profiling and sialyltransferase analysis. Functional studies revealed that both global and \u03b12,6-specific sialylation inhibition markedly compromised the pro-angiogenic capacity of the epicardial secretome, reducing the in vitro tube formation. Our findings indicate that ST6GAL1-dependent \u03b12,6-sialylation is required to activate the pro-angiogenic potential of the epicardial secretome. These data also suggest that glycosylation is a modifiable response to ischemic injury, offering a new therapeutic target for enhancing tissue repair.<\/jats:p>","DOI":"10.1242\/bio.062479","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:32:52Z","timestamp":1777451572000},"source":"Crossref","is-referenced-by-count":0,"title":["Severe hypoxia drives loss of ST6GAL1-mediated \u03b12,6-sialylation in the epicardial secretome impairing angiogenic activity"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5283-1648","authenticated-orcid":false,"given":"Junqing","family":"Zhang","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8987-4158","authenticated-orcid":false,"given":"Harry J.","family":"Whitwell","sequence":"additional","affiliation":[{"name":"Imperial College London 2 Section of Bioanalytical Chemistry, Division of Systems Medicine, Faculty of Medicine , , London W12 0NN ,","place":["United Kingdom"]},{"name":"National Phenome Centre and Imperial Clinical Phenotyping Centre 3 , Department of Metabolism, Digestion and Reproduction , , London W12 0NN ,","place":["United Kingdom"]},{"name":"Imperial College London 3 , Department of Metabolism, Digestion and Reproduction , , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-0702","authenticated-orcid":false,"given":"Costanza","family":"Emanueli","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7150-4615","authenticated-orcid":false,"given":"Pilar","family":"Ruiz-Lozano","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["United Kingdom"]},{"name":"Regencor, Inc 4 , California 94070 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"2026042904322876000_BIO062479C1","doi-asserted-by":"publisher","first-page":"H1509","DOI":"10.1152\/ajpheart.00449.2016","article-title":"Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration","volume":"311","author":"Bellio","year":"2016","journal-title":"Am. 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