{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T08:03:09Z","timestamp":1774598589658,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,6,20]],"date-time":"2018-06-20T00:00:00Z","timestamp":1529452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cluster of Excellence Rebirth","award":["EXC 62\/1"],"award-info":[{"award-number":["EXC 62\/1"]}]},{"name":"Clinical Research Unit 311","award":["HE 3658\/13-1"],"award-info":[{"award-number":["HE 3658\/13-1"]}]},{"name":"Clinical Research Unit 311","award":["GR 3993\/3-1"],"award-info":[{"award-number":["GR 3993\/3-1"]}]},{"name":"Heisenberg Program","award":["HE 3658\/6-1"],"award-info":[{"award-number":["HE 3658\/6-1"]}]},{"name":"Heisenberg Program","award":["HE 3658\/6-2"],"award-info":[{"award-number":["HE 3658\/6-2"]}]},{"name":"Heisenberg Program","award":["HE3658\/14-1"],"award-info":[{"award-number":["HE3658\/14-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodelling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiomyocyte intracellular signalling proteins inducing pathological hypertrophy, therapeutic approaches to target these molecules are currently unavailable. In this study, we aimed to establish and test a therapeutic tool to counteract the 22\u2009kDa calcium and integrin binding protein (CIB) 1, which we have previously identified as nodal regulator of pathological cardiac hypertrophy and as activator of the maladaptive calcineurin\/NFAT axis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Among three different sequences, we selected a shRNA construct (shCIB1) to specifically down-regulate CIB1 by 50% upon adenoviral overexpression in neonatal rat cardiomyocytes (NRCM), and upon overexpression by an adeno-associated-virus (AAV) 9 vector in mouse hearts. Overexpression of shCIB1 in NRCM markedly reduced cellular growth, improved contractility of bioartificial cardiac tissue and reduced calcineurin\/NFAT activation in response to hypertrophic stimulation. In mice, administration of AAV-shCIB1 strongly ameliorated eccentric cardiac hypertrophy and cardiac dysfunction during 2 weeks of pressure overload by transverse aortic constriction (TAC). Ultrastructural and molecular analyses revealed markedly reduced myocardial fibrosis, inhibition of hypertrophy associated gene expression and calcineurin\/NFAT as well as ERK MAP kinase activation after TAC in AAV-shCIB1 vs. AAV-shControl treated mice. During long-term exposure to pressure overload for 10\u2009weeks, AAV-shCIB1 treatment maintained its anti-hypertrophic and anti-fibrotic effects, but cardiac function was no longer improved vs. AAV-shControl treatment, most likely resulting from a reduction in myocardial angiogenesis upon downregulation of CIB1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Inhibition of CIB1 by a shRNA-mediated gene therapy potently inhibits pathological cardiac hypertrophy and fibrosis during pressure overload. While cardiac function is initially improved by shCIB1, this cannot be kept up during persisting overload.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvy154","type":"journal-article","created":{"date-parts":[[2018,6,17]],"date-time":"2018-06-17T15:06:19Z","timestamp":1529247979000},"page":"71-82","source":"Crossref","is-referenced-by-count":17,"title":["A gene therapeutic approach to inhibit calcium and integrin binding protein 1 ameliorates maladaptive remodelling in pressure overload"],"prefix":"10.1093","volume":"115","author":[{"given":"Andrea","family":"Grund","sequence":"first","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Szaroszyk","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina K","family":"D\u00f6ppner","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona","family":"Malek Mohammadi","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"},{"name":"Abteilung f\u00fcr Herz- und Kreislaufforschung, European Center for Angioscience (ECAS), Medizinische Fakult\u00e4t Mannheim, Universit\u00e4t Heidelberg, Ludolf-Krehl-Stra\u00dfe 7-11, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badder","family":"Kattih","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"},{"name":"Abteilung f\u00fcr Herz- und Kreislaufforschung, European Center for Angioscience (ECAS), Medizinische Fakult\u00e4t Mannheim, Universit\u00e4t Heidelberg, Ludolf-Krehl-Stra\u00dfe 7-11, Mannheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mortimer","family":"Korf-Klingebiel","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Gigina","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Scherr","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr H\u00e4matologie, H\u00e4mostaseologie, Onkologie und Stammzelltransplantation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Kensah","sequence":"additional","affiliation":[{"name":"Leibniz Forschungslaboratorien f\u00fcr Biotechnologie und k\u00fcnstliche Organe, Klinik f\u00fcr Herz-, Thorax-, Transplantations- und Gef\u00e4\u00dfchirurgie"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Jara-Avaca","sequence":"additional","affiliation":[{"name":"Leibniz Forschungslaboratorien f\u00fcr Biotechnologie und k\u00fcnstliche Organe, Klinik f\u00fcr Herz-, Thorax-, Transplantations- und Gef\u00e4\u00dfchirurgie"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ina","family":"Gruh","sequence":"additional","affiliation":[{"name":"Leibniz Forschungslaboratorien f\u00fcr Biotechnologie und k\u00fcnstliche Organe, Klinik f\u00fcr Herz-, Thorax-, Transplantations- und Gef\u00e4\u00dfchirurgie"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Martin","sequence":"additional","affiliation":[{"name":"Leibniz Forschungslaboratorien f\u00fcr Biotechnologie und k\u00fcnstliche Organe, Klinik f\u00fcr Herz-, Thorax-, Transplantations- und Gef\u00e4\u00dfchirurgie"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai C","family":"Wollert","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Gohla","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Pharmakologie und Toxikologie and Rudolf Virchow Zentrum f\u00fcr Experimentelle Biomedizin, Universit\u00e4t W\u00fcrzburg, Versbacher Stra\u00dfe 9, W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo A","family":"Katus","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Angiologie und Pneumologie, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg, Mannheim, Im Neuenheimer Feld 410, Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver J","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie, Angiologie und Pneumologie, Universit\u00e4tsklinikum Heidelberg, Im Neuenheimer Feld 410, Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg, Mannheim, Im Neuenheimer Feld 410, Heidelberg, Germany"},{"name":"Klinik f\u00fcr Innere Medizin III, Universit\u00e4tsklinikum Schleswig-Holstein, Arnold-Heller-Stra\u00dfe 3, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, Hannover, Germany"},{"name":"Cluster of Excellence-Rebirth, Medizinische Hochschule Hannover, Carl-Neuberg-Stra\u00dfe 1, Hannover, 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