{"id":107445,"date":"2025-05-13T18:41:53","date_gmt":"2025-05-13T22:41:53","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107445"},"modified":"2026-05-22T17:01:05","modified_gmt":"2026-05-22T21:01:05","slug":"disruption-of-the-uty-epigenetic-regulator-locus-in-hematopoietic-cells-phenocopies-the-profibrotic-attributes-of-y-chromosome-loss-in-heart-failure","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2025\/05\/13\/disruption-of-the-uty-epigenetic-regulator-locus-in-hematopoietic-cells-phenocopies-the-profibrotic-attributes-of-y-chromosome-loss-in-heart-failure\/","title":{"rendered":"Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure"},"content":{"rendered":"

UVA Author:<\/strong> Nicholas Chavkin
\nCitation:<\/strong> Horitani K, Chavkin NW, Arai Y, Wang Y, Ogawa H, Yura Y, Evans MA, Cochran JD, Thel MC, Polizio AH, Sano M, Miura-Yura E, Arai Y, Doviak H, Arnold AP, Gelfand BD, Hirschi KK, Sano S, Walsh K. Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure. Nat Cardiovasc Res. 2024 Mar;3(3):343-355. doi: 10.1038\/s44161-024-00441-z. Epub 2024 Mar 8. PMID: 39183958; PMCID: PMC11343478.<\/p>\n

DOI:<\/strong> https:\/\/doi.org\/10.1038\/s44161-024-00441-z<\/a>
\nPub-Med Number<\/strong>: 39183958<\/p>\n

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Heart failure affects millions of people worldwide, with men exhibiting a higher incidence than women. Our previous work has shown that mosaic loss of the Y chromosome (LOY) in leukocytes is causally associated with an increased risk for heart failure. Here, we show that LOY macrophages from the failing hearts of humans with dilated cardiomyopathy exhibit widespread changes in gene expression that correlate with cardiac fibroblast activation. Moreover, we identify the ubiquitously transcribed t et ratricopeptide Y-linked (Uty<\/i>) gene in leukocytes as a causal locus for an accelerated progression of heart failure in male mice with LOY. We demonstrate that\u00a0Uty<\/i>\u00a0disruption leads to epigenetic alterations in both monocytes and macrophages, increasing the propensity of differentiation into profibrotic macrophages. Treatment with a transforming growth factor-\u03b2-neutralizing antibody prevented the cardiac pathology associated with\u00a0Uty<\/i>\u00a0deficiency in leukocytes. These findings shed light on the mechanisms that contribute to the higher incidence of heart failure in men.<\/p>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

UVA Author: Nicholas Chavkin Citation: Horitani K, Chavkin NW, Arai Y, Wang Y, Ogawa H, Yura Y, Evans MA, Cochran JD, Thel MC, Polizio AH, Sano M, Miura-Yura E, Arai Y, Doviak H, Arnold AP, Gelfand BD, Hirschi KK, Sano S, Walsh K. Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the […]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[22],"class_list":["post-107445","post","type-post","status-publish","format-standard","hentry","category-featured-publications","tag-intranet"],"acf":false,"yoast_head":"\nDisruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2025\/05\/13\/disruption-of-the-uty-epigenetic-regulator-locus-in-hematopoietic-cells-phenocopies-the-profibrotic-attributes-of-y-chromosome-loss-in-heart-failure\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Disruption of the Uty epigenetic regulator locus in hematopoietic cells phenocopies the profibrotic attributes of Y chromosome loss in heart failure - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: Nicholas Chavkin Citation: Horitani K, Chavkin NW, Arai Y, Wang Y, Ogawa H, Yura Y, Evans MA, Cochran JD, Thel MC, Polizio AH, Sano M, Miura-Yura E, Arai Y, Doviak H, Arnold AP, Gelfand BD, Hirschi KK, Sano S, Walsh K. 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