{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:56:15Z","timestamp":1792803375551,"version":"4.5.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"1","funder":[{"name":"Ontario Heart and Stroke Foundation","award":["NA-6736"],"award-info":[{"award-number":["NA-6736"]}]},{"name":"Ontario Heart and Stroke Foundation","award":["NA-7201"],"award-info":[{"award-number":["NA-7201"]}]},{"name":"Canada Research Chair in Matrix Dynamics"},{"name":"CIHR New Investigator Award"},{"name":"The National Association for Public Health","award":["1972"],"award-info":[{"award-number":["1972"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>\n                    Excessive cardiac interstitial fibrosis impairs normal cardiac function. We have shown that the \u03b111\u03b21 (\u03b111) integrin mediates fibrotic responses to glycated collagen in rat myocardium by a pathway involving transforming growth factor-\u03b2. Little is known of the role of the \u03b111 integrin in the developing mammalian heart. Therefore, we examined the impact of deletion of the \u03b111 integrin in wild-type mice and in mice treated with streptozotocin (STZ) to elucidate the role of the \u03b111 integrin in normal cardiac homeostasis and in the pathogenesis of diabetes-related fibrosis. As anticipated, cardiac fibrosis was reduced in \u03b111 integrin knockout mice (\u03b111\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ; C57BL\/6 background) treated with STZ compared with STZ-treated wild-type mice ( P &lt; 0.05). Unexpectedly, diastolic function was impaired in both vehicle and STZ-treated \u03b111\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, as shown by the decreased minimum rate of pressure change and prolonged time constant of relaxation in association with increased end-diastolic pressure (all P &lt; 0.05 compared with wild-type mice). Accordingly, we examined the phenotype of untreated \u03b111\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, which demonstrated a reduced cardiomyocyte cross-sectional cell area and myofibril thickness (all P &lt; 0.05 compared with wild-type mice) and impaired myofibril arrangement. Immunostaining for desmin and connexin 43 showed abnormal intermediate filament organization at intercalated disks and impaired gap-junction development. Overall, deletion of the \u03b111 integrin attenuates cardiac fibrosis in the mammalian mouse heart and reduces ECM formation as a result of diabetes. Furthermore, \u03b111 integrin deletion impairs cardiac function and alters cardiomyocyte morphology. These findings shed further light on the poorly understood interaction between the fibroblast\u2013cardiomyocyte and the ECM.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00918.2015","type":"journal-article","created":{"date-parts":[[2016,5,14]],"date-time":"2016-05-14T00:44:29Z","timestamp":1463186669000},"page":"H96-H106","source":"Crossref","is-referenced-by-count":44,"title":["The \u03b111 integrin mediates fibroblast\u2013extracellular matrix\u2013cardiomyocyte interactions in health and disease"],"prefix":"10.1152","volume":"311","author":[{"given":"Robert A.","family":"Civitarese","sequence":"first","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Talior-Volodarsky","sequence":"additional","affiliation":[{"name":"Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Desjardins","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golam","family":"Kabir","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Switzer","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Kapus","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"McCulloch","sequence":"additional","affiliation":[{"name":"Matrix Dynamics Group, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Gullberg","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A.","family":"Connelly","sequence":"additional","affiliation":[{"name":"Keenan Research Center for Biomedical Science, St. Michael's Hospital and University of 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