{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:30:32Z","timestamp":1788496232183,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cardiac fibrosis (CF) is a major complication of myocardial infarction (MI), impairing myocardial function and leading to heart failure. Rosmarinic acid (RA) exhibits cardioprotective and antifibrotic properties, representing a promising therapeutic strategy for CF. This study evaluated the efficacy of exosomes derived from RA\u2010primed adipose\u2010derived stem cells (ADSCs), focusing on how RA\u2010priming enhances their antioxidant and antifibrotic capacity against CF. An Isoproterenol (ISO)\u2010induced myocardial injury model was established in\u00a0vitro and in\u00a0vivo. In\u00a0vitro, H9C2 cardiomyoblasts were first injured with ISO and then treated with either exosomes (Exo) or RA\u2010primed exosomes (RA\u2010MSC\u2010Exo) to assess cell viability and apoptosis. In\u00a0vivo, 48 Wistar rats were divided into six groups: Control, Exo, RA\u2010MSC\u2010Exo, ISO, ISO\u2009+\u2009Exo, and ISO\u2009+\u2009RA\u2010MSC\u2010Exo. We assessed cardiac biomarkers (CK\u2010MB and troponin I), reactive oxygen species (ROS), and total antioxidant capacity (TAC). We performed echocardiographic, molecular (real\u2010time PCR and Western blotting), and histological analyses (Masson's trichrome staining) to evaluate cardiac function, fibrosis signaling pathways (NF\u2010\u03baB, TGF\u2010\u03b21, SMAD3), and collagen deposition. In\u00a0vitro, both Exo and RA\u2010MSC\u2010Exo treatments significantly restored cell viability and reduced apoptosis in ISO\u2010injured H9C2 cells. In\u00a0vivo, both treatments significantly mitigated ISO\u2010induced cardiac injury by reducing cardiac biomarkers, decreasing ROS production, and enhancing TAC levels. These interventions downregulated the expression of NF\u2010\u03baB, TGF\u2010\u03b21, Smad3, and Collagen I, leading to attenuated collagen deposition and improved cardiac function. Our study demonstrates that RA\u2010primed exosomes effectively mitigate CF and improve cardiac function in an ISO\u2010induced myocardial ischemia model. This targeted approach offers a promising therapeutic strategy for managing myocardial injury and its fibrotic complications.<\/jats:p>","DOI":"10.1096\/fj.202501842rr","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:32:58Z","timestamp":1770111178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rosmarinic Acid\u2010Treated Exosomes Modulate\n                    <scp>TGF<\/scp>\n                    \u2010\u03b21\/Smad3 Signaling to Alleviate Cardiac Fibrosis in an In\u00a0Vitro\/In Vivo Model"],"prefix":"10.1096","volume":"40","author":[{"given":"Zahra","family":"Mansouri","sequence":"first","affiliation":[{"name":"Persian Gulf Physiology Research Center, Medical Basic Sciences Research Institute, and Department of Physiology, Faculty of Medicine Ahvaz Jundishapur University of Medical Sciences  Ahvaz 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