{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:06:40Z","timestamp":1788264400841,"version":"build-2803163510"},"reference-count":65,"publisher":"Portland Press Ltd.","issue":"02","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206587\/Z\/17\/Z"],"award-info":[{"award-number":["206587\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:p>Approximately one in every 800 children is born with the severe aneuploid condition of Down syndrome (DS), a trisomy of chromosome 21. Low blood pressure (hypotension) is a common condition associated with DS and can have a significant impact on exercise tolerance and quality of life. Little is known about the factors driving this hypotensive phenotype, therefore therapeutic interventions are limited. Carbonyl reductase 1 (CBR1) is an enzyme contributing to the metabolism of prostaglandins, glucocorticoids, reactive oxygen species and neurotransmitters, encoded by a gene (CBR1) positioned on chromosome 21 with the potential to affect blood pressure. Utilising telemetric blood pressure measurement of genetically modified mice, we tested the hypothesis that CBR1 influences blood pressure and that its overexpression contributes to hypotension in DS by evaluating possible contributing mechanisms in vitro. In a mouse model of DS (Ts65Dn), which exhibits hypotension, CBR1 activity was increased and pharmacological inhibition of CBR1 ed to increased blood pressure. Mice heterozygous null for Cbr1 had reduced CBR1 enzyme activity and elevated blood pressure. Further experiments indicate that the underlying mechanisms include alterations in both sympathetic tone and prostaglandin metabolism. We conclude that CBR1 activity contributes to blood pressure homeostasis and inhibition of CBR1 may present a novel therapeutic opportunity to correct symptomatic hypotension in DS.<\/jats:p>","DOI":"10.1042\/bsr20241636","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T12:49:32Z","timestamp":1737982172000},"page":"157-170","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Carbonyl reductase 1: a novel regulator of blood pressure in Down syndrome"],"prefix":"10.1042","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-3333","authenticated-orcid":false,"given":"Alexandra J.","family":"Malbon","sequence":"first","affiliation":[{"name":"1The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Easter Bush Campus, EH25 9RG, U.K."},{"name":"2The Roslin Institute, The University of Edinburgh, Easter Bush Campus, EH25 9RG, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Czopek","sequence":"additional","affiliation":[{"name":"3Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Beekman","sequence":"additional","affiliation":[{"name":"4School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk, NR4 7TJ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb R.","family":"Goddard","sequence":"additional","affiliation":[{"name":"4School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk, NR4 7TJ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Boyle","sequence":"additional","affiliation":[{"name":"5Department of Animal and Veterinary Sciences, Scotland\u2019s Rural College, Roslin 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P.","family":"Simpson","sequence":"additional","affiliation":[{"name":"6Mass Spectrometry Core, Edinburgh Clinical Research Facility, Queen\u2019s Medical Research Institute, University of Edinburgh, EH16 4TJ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie Z.","family":"Homer","sequence":"additional","affiliation":[{"name":"3Centre for Cardiovascular Science, The Queen\u2019s Medical Research Institute, The University of Edinburgh, Edinburgh, EH16 4TJ, U.K."},{"name":"6Mass Spectrometry Core, Edinburgh Clinical Research Facility, Queen\u2019s Medical Research Institute, University of Edinburgh, EH16 4TJ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Walker","sequence":"additional","affiliation":[{"name":"7Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, 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