{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:04:45Z","timestamp":1791576285592,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T00:00:00Z","timestamp":1329955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50 HL077107"],"award-info":[{"award-number":["P50 HL077107"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK067532"],"award-info":[{"award-number":["R01 DK067532"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p>\n                    Thrombospondin\u20104 (TSP\u20104) expression increases dramatically in hypertrophic and failing hearts in rodent models and in humans. The aim of this study was to address the function of TSP\u20104 in the heart. TSP\u20104\u2010knockout\n                    <jats:italic>\n                      (Thbs4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                      )\n                    <\/jats:italic>\n                    and wild\u2010type (WT) mice were subjected to transverse aortic constriction (TAC) to increase left ventricle load. After 2 wk,\n                    <jats:italic>\n                      Thbs4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice had a significantly higher heart weight\/body weight ratio than WT mice. The additional increase in the heart weight in TAC\n                    <jats:italic>\n                      Thbs4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice was due to increased deposition of extracellular matrix (ECM). The levels of interstitial collagens were higher in the knockout mice, but the size of cardiomyocytes and apoptosis in the myocardium was unaffected by TSP\u20104 deficiency, suggesting that increased reactive fibrosis was the primary cause of the higher heart weight. The increased ECM deposition in\n                    <jats:italic>\n                      Thbs4\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice was accompanied by changes in functional parameters of the heart and decreased vessel density. The expression of inflammatory and fibrotic genes known to be influential in myocardial remodeling changed as a result of TSP\u20104 deficiency\n                    <jats:italic>in vivo<\/jats:italic>\n                    and as a result of incubation of cells with recombinant TSP\u20104\n                    <jats:italic>in vitro.<\/jats:italic>\n                    Thus, TSP\u20104 is involved in regulating the adaptive responses of the heart to pressure overload, suggesting its important role in myocardial remodeling. Our study showed a direct influence of TSP\u20104 on heart function and to identify the mechanism of its effects on heart remodeling.\u2014Frolova, E. G., Sopko, N., Blech, L., Popovi\u0107, Z. B., Li, J., Vasanji, A., Drumm, C., Krukovets, I., Jain, M. K., Penn, M. S., Plow, E. F., Stenina, O. I. Thrombospondin\u20104 regulates fibrosis and remodeling of the myocardium in response to pressure overload.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 2363\u20102373 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-190728","type":"journal-article","created":{"date-parts":[[2012,2,24]],"date-time":"2012-02-24T01:06:34Z","timestamp":1330045594000},"page":"2363-2373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Thrombospondin\u20104 regulates fibrosis and remodeling of the myocardium in response to pressure overload"],"prefix":"10.1096","volume":"26","author":[{"given":"Ella G.","family":"Frolova","sequence":"first","affiliation":[{"name":"Department of Molecular Cardiology Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"},{"name":"Joseph J. Jacob Center for Thrombosis and Vascular Biology Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Sopko","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Blech","sequence":"additional","affiliation":[{"name":"Department of Molecular Cardiology Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"},{"name":"Joseph J. Jacob Center for Thrombosis and Vascular Biology Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran B.","family":"Popovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Vasanji","sequence":"additional","affiliation":[{"name":"Biomedical Imaging and Analysis Core Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Drumm","sequence":"additional","affiliation":[{"name":"Department of Molecular Cardiology Case Western Reserve University School of Medicine Cleveland Clinic Cleveland Ohio USA"},{"name":"Joseph J. 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