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despite advances in treatment. Excessive myocardial fibrosis plays a vital role in the development of adverse cardiac remodeling and deterioration of cardiac function. Understanding the molecular and cellular mechanism of the fibrosis process and developing effective therapeutics are of great importance.<jats:italic>Salvia miltiorrhiza<\/jats:italic>and<jats:italic>Carthamus tinctorius<\/jats:italic>extract (SCE) is indicated for angina pectoris and other ischemic cardiovascular diseases in China. SCE has been shown to inhibit the platelet activation and aggregation, ameliorate ROS-induced myocardial necrosis by inhibiting mitochondrial permeability transition pore opening, and promote angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). However, whether SCE has effect on cardiac fibrosis after MI is not fully clear. Here, a mouse model of MI was established to observe the effect of SCE upon survival, cardiac function, myocardial fibrosis, and inflammation. Quantitative PCR and western blot assays were used to determine the expression of genes related to transforming growth factor-<jats:italic>\u03b2<\/jats:italic>(TGF-<jats:italic>\u03b2<\/jats:italic>) cascade and inflammatory responses<jats:italic>in vivo<\/jats:italic>. Additionally, the effects of SCE upon the collagen production, TGF-<jats:italic>\u03b2<\/jats:italic>\/Smad3 (SMAD family member 3) signaling, and the levels of histone methylation in primary cardiac fibroblasts were detected. We found that SCE treatment significantly improved survival and left ventricular function in mice after MI. Inhibition of inflammation and fibrosis, as well as decreased expression of Smad3, was observed with SCE treatment. In TGF-<jats:italic>\u03b2<\/jats:italic>-stimulated cardiac fibroblasts, SCE significantly decreased the expression of collagen,<jats:italic>\u03b1<\/jats:italic>-smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>-SMA), and Smad3. Furthermore, SCE treatment downregulated the levels of H3K4 trimethylation (H3K4me3) and H3K36 trimethylation (H3K36me3) at the<jats:italic>Smad3<\/jats:italic>promoter region of cardiac fibroblasts, leading to inhibition of<jats:italic>Smad3<\/jats:italic>transcription. Our findings suggested that SCE prevents myocardial fibrosis and adverse remodeling after MI with a novel mechanism of suppressing histone methylation of the<jats:italic>Smad3<\/jats:italic>promoter and its transcription.<\/jats:p>","DOI":"10.1155\/2019\/6479136","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T23:30:59Z","timestamp":1559259059000},"page":"1-12","source":"Crossref","is-referenced-by-count":22,"title":["<i>Salvia miltiorrhiza<\/i>and<i>Carthamus tinctorius<\/i>Extract Prevents Cardiac Fibrosis and Dysfunction after Myocardial Infarction by Epigenetically Inhibiting Smad3 Expression"],"prefix":"10.1155","volume":"2019","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, 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