{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:49:46Z","timestamp":1791154186024,"version":"4.1.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2013,4,17]],"date-time":"2013-04-17T00:00:00Z","timestamp":1366156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>Fibroblast activity promotes adverse left ventricular (LV) remodeling that underlies the development of ischemic cardiomyopathy. Transforming growth factor-\u03b2 (TGF-\u03b2) is a potent stimulus for fibrosis, and the extracellular signal-regulated kinases(ERK) 1\/2 pathway also contributes to the fibrotic response. The thrombin receptor, protease-activated receptor 1 (PAR1), has been shown to play an important role in the excessive fibrosis in different tissues. The aim of this study was to investigate the influence of a PAR1 inhibitor, SCH79797, on cardiac fibrosis, tissue stiffness and postinfarction remodeling, and effects of PAR1 inhibition on thrombin-induced TGF-\u03b2 and (ERK) 1\/2 activities in cardiac fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We used a rat model of myocardial ischemia\u2013reperfusion injury, isolated cardiac fibroblasts, and 3-dimensional (3D) cardiac tissue models fabricated to ascertain the contribution of PAR1 activation on cardiac fibrosis and LV remodeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The PAR1 inhibitor attenuated LV dilation and improved LV systolic function of the reperfused myocardium at 28 days. This improvement was associated with a nonsignificant decrease in scar size (%LV) from 23 \u00b1 % in the control group (n = 10) to 16% \u00b1 5.5% in the treated group (n = 9; P = .052). In the short term, the PAR1 inhibitor did not rescue infarct size or LV systolic function after 3 days. The PAR1 inhibition abolished thrombin-mediated ERK1\/2 phosphorylation, TGF-\u03b2 and type I procollagen production, matrix metalloproteinase-2\/9 activation, myofibroblasts transformation in vitro, and abrogated the remodeling of 3D tissues induced by chronic thrombin treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These studies suggest PAR1 inhibition initiated after ischemic injury attenuates adverse LV remodeling through late-stage antifibrotic events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1074248413485434","type":"journal-article","created":{"date-parts":[[2013,4,18]],"date-time":"2013-04-18T21:48:56Z","timestamp":1366321736000},"page":"460-475","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":64,"title":["Protease-Activated Receptor 1 Inhibition by SCH79797 Attenuates Left Ventricular Remodeling and Profibrotic Activities of Cardiac Fibroblasts"],"prefix":"10.1177","volume":"18","author":[{"given":"Dmitry L.","family":"Sonin","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, USA"},{"name":"V.A. 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