{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:58:31Z","timestamp":1781971111865,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,9,25]],"date-time":"2008-09-25T00:00:00Z","timestamp":1222300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mice genetically modified to produce low levels (\u223c1% of wild\u2010type) of coagulation FVII presented with echocardiographic evidence of heart abnormalities. Decreases in ventricular size and reductions in systolic and diastolic functions were found, suggestive of a restrictive cardiomyopathy and consistent with an infiltrative myopathic process. Microscopic analysis of mouse hearts showed severe patchy fibrosis in the low\u2010FVII mice. Haemosiderin deposition was discovered in hearts of these mice, along with increases in inflammatory cell number, ultimately resulting in widespread collagen deposition. Significant increases in mRNA levels of TGF\u03b2, TNF\u03b1 and several matrix metalloproteinases in low\u2010FVII mice, beginning at early ages, supported a state of cardiac remodelling associated with the fibrotic pathology. Mechanistic time\u2010course studies suggested that cardiac fibrosis in low\u2010FVII mice originated from bleeding in heart tissue, resulting in the recruitment of leukocytes, which released inflammatory mediators and induced collagen synthesis and secretion. These events led to necrosis of cardiomyocytes and collagen deposition, characteristics of cardiac fibrosis. The results of this study demonstrated that haemorrhagic and inflammatory responses to a severe FVII deficiency resulted in the development of cardiac fibrosis, observed echocardiographically as a restrictive cardiomyopathy, with compromised ventricular diastolic and systolic functions. Copyright \u00a9 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2454","type":"journal-article","created":{"date-parts":[[2008,9,25]],"date-time":"2008-09-25T05:08:15Z","timestamp":1222319295000},"page":"362-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Severe deficiency of coagulation Factor VII results in spontaneous cardiac fibrosis in mice"],"prefix":"10.1002","volume":"217","author":[{"given":"H","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Noria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MJ","family":"Sandoval\u2010Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Menchen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DL","family":"Donahue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VA","family":"Ploplis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FJ","family":"Castellino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6258"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/383073a0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V88.5.1583.1583"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/36862"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.242501899"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH05-05-0337"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000141427.61023.f4"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1540-8167.2004.03625.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1067\/mje.2002.120892"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2073"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2456"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-09-3780"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63949-1"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00845.2001"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6580"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/107155760000700606"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-04-1130"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2454","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:36:05Z","timestamp":1761050165000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,30]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,2]]}},"alternative-id":["10.1002\/path.2454"],"URL":"https:\/\/doi.org\/10.1002\/path.2454","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,30]]},"assertion":[{"value":"2008-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-10-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}