The incidence of cardiac dysfunction after
myocardial infarction (MI) continues to increase 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. Salvia miltiorrhiza and
Carthamus tinctorius 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-β (TGF-β) cascade and inflammatory responses in vivo. Additionally, the effects of SCE upon the
collagen production, TGF-β/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-β-stimulated cardiac fibroblasts, SCE significantly decreased the expression of
collagen, α-smooth muscle actin (α-SMA), and Smad3. Furthermore, SCE treatment downregulated the levels of H3K4 trimethylation (
H3K4me3) and H3K36 trimethylation (H3K36me3) at the Smad3 promoter region of cardiac fibroblasts, leading to inhibition of Smad3 transcription. Our findings suggested that SCE prevents myocardial
fibrosis and adverse remodeling after MI with a novel mechanism of suppressing
histone methylation of the Smad3 promoter and its transcription.