{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:28:56Z","timestamp":1788406136225,"version":"build-2803163510"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The \u2018Cardiovascular\u2010Kidney\u2010Metabolic Syndrome\u2019 which is characterized by multi\u2010organ dysfunction ultimately resulting in adverse cardiac outcomes, serves to highlight the importance of organ crosstalk in pathophysiology. The cellular metabolism of fructose, regulated by Ketohexokinase\u2010C with associated inflammatory sequelae, is mechanistically linked with each component of this clinical entity. Fructose metabolism is confined to the Kidney, Liver, and Small Intestine under normal physiological conditions; however, in the context of ischaemia, HIF\u20101\u03b1 induces cardiac expression of Ketohexokinase\u2010C with consequent organ hypertrophy and dysfunction. This adverse effect of cardiac HIF\u20101\u03b1 accumulation raises concerns over the potential pleiotropic effects of the \u2018HIF stabilizing\u2019 inhibitors of Prolyl Hydroxylase currently entering clinical practice for the treatment of anemia in Chronic Kidney Disease, particularly given the increased cardiovascular mortality observed in this patient group. We suggest that pleiotropic effects of \u2018HIF stabilization\u2019 on cardiac physiology warrant investigation and, furthermore, that pharmacological inhibition of Ketohexokinase\u2010C, and therefore fructose metabolism, represents an opportunity to improve cardiac outcomes in the Cardiovascular\u2010Kidney\u2010Metabolic Syndrome.<\/jats:p>","DOI":"10.1002\/cph4.70033","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T03:13:29Z","timestamp":1754968409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>HIF<\/scp>\u2010Mediated Fructose Metabolism and Disease Progression in the Cardiovascular\u2010Kidney\u2010Metabolic Syndrome"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2743-2235","authenticated-orcid":false,"given":"David","family":"Mathew","sequence":"first","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Davidson","sequence":"additional","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Yellon","sequence":"additional","affiliation":[{"name":"The Hatter Cardiovascular Institute University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14181"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008060576"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00715"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.25.2.353"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medj.2021.04.007"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.36.187.273"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60674-5"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14508"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.922427"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001184"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395\u2010024\u201001094\u20106"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.advnut.2022.12.002"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105020"}],"container-title":["Comprehensive Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T12:02:08Z","timestamp":1756209728000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cph4.70033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/cph4.70033"],"URL":"https:\/\/doi.org\/10.1002\/cph4.70033","archive":["Portico"],"relation":{},"ISSN":["2040-4603","2040-4603"],"issn-type":[{"value":"2040-4603","type":"print"},{"value":"2040-4603","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70033"}}