Connective tissue growth factor inhibition enhances cardiac repair and limits fibrosis after myocardial infarction
Vainio, Laura E.; Szabó, Zoltán; Lin, Ruizhu; Ulvila, Johanna; Yrjölä, Raisa; Alakoski, Tarja; Piuhola, Jarkko; Koch, Walter J.; Ruskoaho, Heikki; Fouse, Shaun D.; Seeley, Todd W.; Gao, Erhe; Signore, Pierre; Lipson, Kenneth E.; Magga, Johanna; Kerkelä, Risto (2019-02-25)
Laura E. Vainio, Zoltán Szabó, Ruizhu Lin, Johanna Ulvila, Raisa Yrjölä, Tarja Alakoski, Jarkko Piuhola, Walter J. Koch, Heikki Ruskoaho, Shaun D. Fouse, Todd W. Seeley, Erhe Gao, Pierre Signore, Kenneth E. Lipson, Johanna Magga, Risto Kerkelä, Connective Tissue Growth Factor Inhibition Enhances Cardiac Repair and Limits Fibrosis After Myocardial Infarction, JACC: Basic to Translational Science, Volume 4, Issue 1, 2019, Pages 83-94, ISSN 2452-302X, https://doi.org/10.1016/j.jacbts.2018.10.007
© 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
https://urn.fi/URN:NBN:fi-fe2020040913542
Tiivistelmä
Summary
Myocardial infarction (MI)−induced cardiac fibrosis attenuates cardiac contractile function, and predisposes to arrhythmias and sudden cardiac death. Expression of connective tissue growth factor (CTGF) is elevated in affected organs in virtually every fibrotic disorder and in the diseased human myocardium. Mice were subjected to treatment with a CTGF monoclonal antibody (mAb) during infarct repair, post-MI left ventricular (LV) remodeling, or acute ischemia−reperfusion injury. CTGF mAb therapy during infarct repair improved survival and reduced LV dysfunction, and reduced post-MI LV hypertrophy and fibrosis. Mechanistically, CTGF mAb therapy induced expression of cardiac developmental and/or repair genes and attenuated expression of inflammatory and/or fibrotic genes.
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