{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:08:00Z","timestamp":1792192080220,"version":"4.4.0"},"reference-count":139,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"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\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Grant\u2014148401"],"award-info":[{"award-number":["Grant\u2014148401"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["18-0022032"],"award-info":[{"award-number":["18-0022032"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2018 Research Grant of the Spanish Fundaci\u00f3n Alfonso Mart\u00edn Escudero"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Atrial fibrillation (AF) is an important clinical problem. Chronic pressure\/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the key cell type responsible for ECM production. The primary purpose of this article is to review the evidence regarding direct effects of stretch on cardiac fibroblasts, specifically: (i) the similarities and differences among studies in observed effects of stretch on cardiac fibroblast function; (ii) the signalling pathways implicated; and (iii) the factors that affect stretch-related phenotypes. Our review summarizes the most important findings and limitations in this area and gives an overview of clinical data and animal models related to cardiac stretch, with particular emphasis on the atria. We suggest that the evidence regarding direct fibroblast activation by stretch is weak and inconsistent, in part because of variability among studies in key experimental conditions that govern the results. Further work is needed to clarify whether, in fact, stretch induces direct activation of cardiac fibroblasts and if so, to elucidate the determining factors to ensure reproducible results. If mechanical load on fibroblasts proves not to be clearly profibrotic by direct actions, other mechanisms like paracrine influences, the effects of systemic mediators and\/or the direct consequences of myocardial injury or death, might account for the link between cardiac stretch and fibrosis. Clarity in this area is needed to improve our understanding of AF pathophysiology and assist in therapeutic development.<\/jats:p>","DOI":"10.1093\/cvr\/cvab035","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T03:47:04Z","timestamp":1612928824000},"page":"440-460","source":"Crossref","is-referenced-by-count":38,"title":["The effects of cardiac stretch on atrial fibroblasts: analysis of the evidence and potential role in atrial fibrillation"],"prefix":"10.1093","volume":"118","author":[{"given":"Xixiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute, Montreal, Canada"},{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Garcia-Elias","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Benito","sequence":"additional","affiliation":[{"name":"Vascular Biology and Metabolism Program, Vall d\u2019Hebr\u00f3n Research Institute (VHIR), Barcelona, Spain"},{"name":"Cardiology Department, Hospital Universitari Vall d\u2019Hebr\u00f3n, Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5565-3311","authenticated-orcid":false,"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute, Montreal, Canada"},{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada"},{"name":"Department of Pharmacology and Physiology of the Universit\u00e9 de Montr\u00e9al Faculty of Medicine, Montreal, Canada"},{"name":"Institute of Pharmacology, West German Heart and 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