{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:59:43Z","timestamp":1791190783136,"version":"4.1.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,8,29]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The cellular and molecular basis for post\u2013myocardial infarction (MI) structural and functional remodeling is not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Our aim was to determine if Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx through transient receptor potential canonical (TRPC) channels contributes to post-MI structural and functional remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      TRPC1\/3\/4\/6 channel mRNA increased after MI in mice and was associated with TRPC-mediated Ca\n                      <jats:sup>2+<\/jats:sup>\n                      entry. Cardiac myocyte\u2013specific expression of a dominant-negative (loss-of-function) TRPC4 channel increased basal myocyte contractility and reduced hypertrophy and cardiac structural and functional remodeling after MI while increasing survival in mice. We used adenovirus-mediated expression of TRPC3\/4\/6 channels in cultured adult feline myocytes to define mechanistic aspects of these TRPC-related effects. TRPC3\/4\/6 overexpression in adult feline myocytes induced calcineurin (Cn)-nuclear factor of activated T-cells (NFAT)\u2013mediated hypertrophic signaling, which was reliant on caveolae targeting of TRPCs. TRPC3\/4\/6 expression in adult feline myocytes increased rested state contractions and increased spontaneous sarcoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      sparks mediated by enhanced phosphorylation of the ryanodine receptor. TRPC3\/4\/6 expression was associated with reduced contractility and response to catecholamines during steady-state pacing, likely because of enhanced sarcoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      leak.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx through TRPC channels expressed after MI activates pathological cardiac hypertrophy and reduces contractility reserve. Blocking post-MI TRPC activity improved post-MI cardiac structure and function.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.115.303831","type":"journal-article","created":{"date-parts":[[2014,7,21]],"date-time":"2014-07-21T21:39:14Z","timestamp":1405978754000},"page":"567-580","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":115,"title":["Transient Receptor Potential Channels Contribute to Pathological Structural and Functional Remodeling After Myocardial Infarction"],"prefix":"10.1161","volume":"115","author":[{"given":"Catherine A.","family":"Makarewich","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Correll","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle M.","family":"Trappanese","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas E.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine D.","family":"Troupes","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remus M.","family":"Berretta","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Kubo","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muniswamy","family":"Madesh","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongwen","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; Department of Pediatrics, University of Cincinnati, Cincinnati Children\u2019s Hospital Medical Center, OH (J.D., R.N.C., J.D.M.); and Howard Hughes Medical Institute, Cincinnati, OH (J.D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery D.","family":"Molkentin","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center (C.A.M., H.Z., D.M.T., C.D.T., R.M.B., H.K., X.C., S.R.H.), Department of Physiology (C.A.M., H.Z., C.D.T., X.C., S.R.H.), Center for Translational Medicine (N.E.H., M.M., E.G.), and Biochemistry Department (N.E.H., M.M.), Temple University School of Medicine, Philadelphia, PA; 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