{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:16:01Z","timestamp":1791656161052,"version":"4.3.4"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of\n                      <jats:italic>O<\/jats:italic>\n                      \u2010linked \u03b2\u2010\n                      <jats:italic>N<\/jats:italic>\n                      acetylglucosamine (\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Using a naturally occurring dominant\u2010negative\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAcase (dnOGA) inducible cardiomyocyte\u2010specific overexpression transgenic mouse model, we induced dnOGA in 8\u2010 to 10\u2010week\u2010old mouse hearts. We examined the effects of 2\u2010week and 24\u2010week dnOGA overexpression, which progressed to a 1.8\u2010fold increase in protein\n                      <jats:italic>O\u2010<\/jats:italic>\n                      GlcNAcylation. Two\u2010week increases in protein\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAc levels did not alter heart weight or function; however, 24\u2010week increases in protein\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAcylation led to cardiac hypertrophy, mitochondrial dysfunction, fibrosis, and diastolic dysfunction. Interestingly, systolic function was maintained in 24\u2010week dnOGA overexpression, despite several changes in gene expression associated with cardiovascular disease. Specifically, mRNA\u2010sequencing analysis revealed several gene signatures, including reduction of mitochondrial oxidative phosphorylation, fatty acid, and glucose metabolism pathways, and antioxidant response pathways after 24\u2010week dnOGA overexpression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This study indicates that moderate increases in cardiomyocyte protein\n                      <jats:italic>O<\/jats:italic>\n                      \u2010GlcNAcylation leads to a differential response with an initial reduction of metabolic pathways (2\u2010week), which leads to cardiac remodeling (24\u2010week). Moreover, the mouse model showed evidence of diastolic dysfunction consistent with a heart failure with preserved ejection fraction. These findings provide insight into the adaptive versus maladaptive responses to increased\n                      <jats:italic>O\u2010<\/jats:italic>\n                      GlcNAcylation in heart.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.029898","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T08:01:09Z","timestamp":1695715269000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Sustained Increases in Cardiomyocyte Protein\n                    <i>O<\/i>\n                    \u2010Linked \u03b2\u2010N\u2010Acetylglucosamine Levels Lead to Cardiac Hypertrophy and Reduced Mitochondrial Function Without Systolic Contractile Impairment"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2617-2698","authenticated-orcid":false,"given":"Chae\u2010Myeong","family":"Ha","sequence":"first","affiliation":[{"name":"Division of Molecular and Cellular Pathology, Department of Pathology University of Alabama at Birmingham Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-6049","authenticated-orcid":false,"given":"Sayan","family":"Bakshi","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Pathology, Department of Pathology University of Alabama at Birmingham Birmingham AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3191-0720","authenticated-orcid":false,"given":"Manoja K.","family":"Brahma","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Pathology, Department of Pathology University of Alabama at 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