Theacrine attenuates myocardial fibrosis after myocardial infarction via the SIRT3/β-catenin/PPARγ pathway in estrogen-deficient mice.

To investigate the role of theacrine in the protection of ventricular remodeling and chronic heart failure after myocardial infarction in the estrogen-deficient mice.Female C57BL/6 mice aged 8 weeks old were selected and then subjected to bilateral oophorectomy. At 7 days after surgery, the models of the myocardial infarction were established by ligating the anterior descending coronary artery. On the first day after myocardial infarction, Theacrine (20 mg/kg) was administered via gavage for continuous 28 days. Thereafter, the cardiac function in each group of mice was detected via cardiac ultrasonography for small animals at 7, 14, and 28 days after surgery. The mice were sacrificed after 28 days. The infarct size of mice was determined through 2,3,5-triphenyltetrazolium chloride (TTC) and Evan blue double staining assay, while the myocardial fibrosis was assessed via Masson staining assay. The expression levels of collagen-related proteins Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), and the transforming growth factor-β (TGF-β) were measured by Western blotting (WB). The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining assay was applied to evaluate the myocardial apoptosis, and the WB was employed to detect apoptosis-associated proteins. The expression level of silent information regulator 2 homologue 3 (SIRT3) protein was detected by immunohistochemistry, and the expression levels of SIRT3, β-catenin and peroxisome proliferator-activated receptor gamma (PPARγ) protein were measured via WB.Compared with those in the Sham group, the ejection fraction (EF) and fractional shortening (FS) in estrogen-deficient mice were significantly lowered, the myocardial fibrosis and myocardial apoptosis were clearly aggravated, and the SIRT3 expression was decreased at 28 days after myocardial infarction. The theacrine could improve the cardiac function after the myocardial infarction in estrogen-deficient mice and relieve both myocardial fibrosis and myocardial apoptosis during chronic remodeling after myocardial infarction in estrogen-deficient mice. After the intervention with theacrine, the estrogen-deficient mice with myocardial infarction had up-regulated SIRT3 and PPARγ levels and a reduced β-catenin level in the heart.Theacrine is able to activate SIRT3 and repress myocardial fibrosis and apoptosis after myocardial infarction in ovariectomized mice, thereby improving the cardiac function of ovariectomized mice with myocardial infarction through the possible downstream signal pathway β-catenin/PPARγ.