{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:30:22Z","timestamp":1789907422356,"version":"4.0.1"},"reference-count":31,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:p> Following myocardial infarction (MI) inflammatory responses transform cardiac fibroblasts to myofibroblasts, which in vitro studies show form heterocellular gap junctions with cardiac myocytes via Connexin43 (Cx43). The ability to form heterocellular junctions in the intact heart and the impact of these junctions on propagation is unclear. We used a canine model of MI and characterized the distribution and quantity of myofibroblasts in surviving epicardial cells [epicardial border zone (EBZ)]. We found a significant increase in myofibroblasts within the EBZ and no gap junction plaques between myofibroblasts and myocytes. Because myofibroblasts produce IL-1\u03b2, which downregulates Cx43, we asked whether myofibroblast proliferation causes loss of Cx43 near myofibroblast clusters. In vitro studies showed that IL-1\u03b2 caused loss of Cx43 and reduced coupling. Western blot showed a significant increase of IL-1\u03b2 in the EBZ, and immunohistochemistry showed a loss of Cx43 in regions of myofibroblasts in the intact heart. Additionally, dye studies in intact heart showed no coupling between myocytes and myofibroblasts. To quantify the effect of myofibroblasts on propagation we used a two-dimensional subcellular computer model of the EBZ, which showed that heterogeneities in myofibroblast density lead to conduction abnormalities. In conclusion, an increase of myofibroblasts in the infarcted heart causes heterogeneous Cx43 levels, possibly as a result of the release of IL-1\u03b2 and decreased cell-cell communication, which leads to conduction abnormalities following MI. <\/jats:p>","DOI":"10.1152\/ajpheart.00498.2011","type":"journal-article","created":{"date-parts":[[2011,11,19]],"date-time":"2011-11-19T05:29:41Z","timestamp":1321680581000},"page":"H790-H800","source":"Crossref","is-referenced-by-count":48,"title":["Myofibroblasts cause heterogeneous Cx43 reduction and are unlikely to be coupled to myocytes in the healing canine infarct"],"prefix":"10.1152","volume":"302","author":[{"given":"Jennifer R.","family":"Baum","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Long","sequence":"additional","affiliation":[{"name":"Departments of 2Nursing and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candido","family":"Cabo","sequence":"additional","affiliation":[{"name":"Computer Systems, New York City College of Technology\/CUNY and Graduate Center\/CUNY, New York; 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