{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T01:20:44Z","timestamp":1775092844859,"version":"3.50.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"23","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,12,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac hypertrophy is an adaptive remodeling event that may improve or diminish contractile performance of the heart. Physiologic and pathologic hypertrophy yield distinct outcomes, yet both are dependent on caspase\u2010directed proteolysis. This suggests that each form of myocardial growth may derive from a specific caspase cleavage event(s). We examined whether caspase 3 cleavage of the actin capping\/severing protein gelsolin is essential for the development of pathologic hypertrophy.<\/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\">Caspase targeting of gelsolin was established through protein analysis of hypertrophic cardiomyocytes and mass spectrometry mapping of cleavage sites. Pathologic agonists induced late\u2010stage caspase\u2010mediated cleavage of gelsolin. The requirement of caspase\u2010mediated gelsolin cleavage for hypertrophy induction was evaluated in primary cardiomyocytes by cell size analysis, monitoring of prohypertrophy markers, and measurement of hypertrophy\u2010related transcription activity. The in\u00a0vivo impact of caspase\u2010mediated cleavage was investigated by echo\u2010guided intramyocardial injection of adenoviral\u2010expressed gelsolin. Expression of the N\u2010terminal gelsolin caspase cleavage fragment was necessary and sufficient to cause pathologic remodeling in isolated cardiomyocytes and the intact heart, whereas expression of a noncleavable form prevents cardiac remodeling. Alterations in myocardium structure and function were determined by echocardiography and end\u2010stage cardiomyocyte cell size analysis. Gelsolin secretion was also monitored for its impact on na\u00efve cells using competitive antibody trapping, demonstrating that hypertrophic agonist stimulation of cardiomyocytes leads to gelsolin secretion, which induces hypertrophy in na\u00efve cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results suggest that cell autonomous caspase cleavage of gelsolin is essential for pathologic hypertrophy and that cardiomyocyte secretion of gelsolin may accelerate this negative remodeling response.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.010404","type":"journal-article","created":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T10:00:18Z","timestamp":1543485618000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Caspase Cleavage of Gelsolin Is an Inductive Cue for Pathologic Cardiac Hypertrophy"],"prefix":"10.1161","volume":"7","author":[{"given":"Charis","family":"Putinski","sequence":"first","affiliation":[{"name":"Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research Regenerative Medicine Program Ottawa Hospital Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Abdul\u2010Ghani","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research Regenerative Medicine Program Ottawa Hospital Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Brunette","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research Regenerative Medicine Program Ottawa Hospital Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick G.","family":"Burgon","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa Ontario Canada"},{"name":"Department of Medicine University of Ottawa Ontario Canada"},{"name":"University of Ottawa Heart Institute Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn A.","family":"Megeney","sequence":"additional","affiliation":[{"name":"Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research Regenerative Medicine Program Ottawa Hospital Ottawa Ontario Canada"},{"name":"Department of Cellular and Molecular Medicine Faculty of Medicine University of Ottawa Ontario Canada"},{"name":"Department of Medicine University of Ottawa Ontario 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