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Immunocytochemical analysis confirmed SULF1\/SULF2 expression not only in endothelial cell lining of blood vessels but also in the developing cardiomyocytes but not in the adult cardiomyocytes despite persisting at reduced levels in the adult endothelial cells. The levels of both SULFs in adult ischemic human hearts and in murine hearts following coronary occlusion increased in endothelial lining of some regional blood vessels but with little or no detection in the cardiomyocytes. Unlike the normal adult heart, the levels of SULF1 and SULF2 were markedly increased in the adult canine right-atrial haemangiosarcoma correlating with increased TGF\u03b2 cell signalling. Cell signalling relationship to ischaemia was further confirmed by in vitro hypoxia of HMec1 endothelial cells demonstrating dynamic changes in not only vegf and its receptors but also sulfotransferases and Sulf1 &amp; Sulf2 levels. In vitro hypoxia of HMec1 cells also confirmed earlier up-regulation of TGF\u03b2 cell signalling revealed by Smad2, Smad3, ALK5 and TGF\u03b21 changes and later down-regulation correlating with Sulf1 but not Sulf2 highlighting Sulf1\/Sulf2 differences in endothelial cells under hypoxia.<\/jats:p>","DOI":"10.1038\/s41598-021-01629-0","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T11:03:51Z","timestamp":1637147031000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modulation of cell signalling and sulfation in cardiovascular development and disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Tiago","family":"Justo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonie","family":"Martiniuc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurtej K.","family":"Dhoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,17]]},"reference":[{"issue":"3","key":"1629_CR1","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/s41390-018-0094-9","volume":"84","author":"AM Rudolph","year":"2018","unstructured":"Rudolph, A. 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