{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:50:55Z","timestamp":1787061055815,"version":"build-2736575974"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,2,21]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The mitochondrial mRNA\u2010binding protein FASTKD1 (Fas\u2010activated\u00a0serine\/threonine\u00a0[FAST] kinase domain\u2013containing protein 1) protects myocytes from oxidative stress in vitro. However, the role of FASTKD1 in the myocardium in vivo is unknown. Therefore, we developed cardiac\u2010specific FASTKD1 transgenic mice to test the effects of this protein on experimental myocardial infarction (MI).<\/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\">Transgenic mouse lines with cardiac myocyte\u2010specific overexpression of FASTKD1 to varying degrees were generated. These mice displayed normal cardiac morphological features and function at the gross and microscopic levels. Isolated cardiac mitochondria from all transgenic mouse lines showed normal mitochondrial function, ATP levels, and permeability transition pore activity. Male nontransgenic and transgenic mice from the highest\u2010expressing line were subjected to 8\u2009weeks of permanent coronary ligation. Of nontransgenic mice, 40% underwent left ventricular free wall rupture within 7\u2009days of MI compared with 0% of FASTKD1\u2010overexpressing mice. At 3\u2009days after MI, FASTKD1 overexpression did not alter infarct size. However, increased FASTKD1 resulted in decreased neutrophil and increased macrophage infiltration, elevated levels of the extracellular matrix component periostin, and enhanced antioxidant capacity compared with control mice. In contrast, markers of mitochondrial fusion\/fission and apoptosis remained unaltered. Instead, transcriptomic analyses indicated activation of the integrated stress response in the FASTKD1 transgenic hearts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac\u2010specific overexpression of FASTKD1 results in viable mice displaying normal cardiac morphological features and function. However, these mice are resistant to MI\u2010induced cardiac rupture and display altered inflammatory, extracellular matrix, and antioxidant responses following MI. Moreover, these protective effects were associated with enhanced activation of the integrated stress response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.025867","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T07:16:51Z","timestamp":1676963811000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiac Myocyte\u2010Specific Overexpression of FASTKD1 Prevents Ventricular Rupture After Myocardial Infarction"],"prefix":"10.1161","volume":"12","author":[{"given":"Kurt D.","family":"Marshall","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula J.","family":"Klutho","sequence":"additional","affiliation":[{"name":"Dalton Cardiovascular Research Center University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihui","family":"Song","sequence":"additional","affiliation":[{"name":"Dalton Cardiovascular Research Center University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajika","family":"Roy","sequence":"additional","affiliation":[{"name":"Dalton Cardiovascular Research Center University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike","family":"Krenz","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology and Physiology University of Missouri Columbia MO"},{"name":"Dalton Cardiovascular Research Center University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4473-3869","authenticated-orcid":false,"given":"Christopher P.","family":"Baines","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Missouri Columbia MO"},{"name":"Department of Medical Pharmacology and Physiology University of Missouri Columbia MO"},{"name":"Dalton Cardiovascular Research Center University of Missouri Columbia MO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000950"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.5.529"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn335"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00370-1"},{"key":"e_1_3_1_6_2","first-page":"291","article-title":"Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats","volume":"148","author":"Hill MF","year":"1996","unstructured":"Hill MF, Singal PK. 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