Cardamonin protects against adverse cardiac remodeling through mTORC1 inhibition in mice with myocardial infarction

• Published in: Pharmazie Vol. 73; no. 9; p. 508
• Main Authors: You, Wei, Wu, Zhiming, Ye, Fei, Wu, Xiangqi
• Format: Journal Article
• Language: English
• Published: Germany 01-09-2018
• Subjects: Animals; Apoptosis - drug effects; Cardiomegaly - prevention & control; Cardiotonic Agents - pharmacology; Chalcones - pharmacology; Echocardiography; In Situ Nick-End Labeling; Male; Mechanistic Target of Rapamycin Complex 1 - antagonists & inhibitors; Mice; Mice, Inbred C57BL; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Phosphorylation - drug effects; Random Allocation; Rats; Signal Transduction - drug effects; Ventricular Remodeling - drug effects
• ISSN: 0031-7144
• DOI: 10.1691/ph.2018.8600

The mTORC1-dependent signaling pathway is mainly involved in the adverse left ventricular remodeling (ALVR) process after myocardial infarction (MI). However, whether mTORC1 inhibition by cardamonin attenuates ALVR after MI is still not reported. Twenty mice were randomly assigned into three groups: sham group (10 ml/kg/day PBS, n=6), model group (MI and 10 ml/kg/day PBS, n=7) and cardamonin-treated group (MI and 20 mg/kg/day cardamonin, n=7). All groups received an intraperitoneal injection accordingly for two weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes and cell apoptosis of border area were evaluated using Masson's staining, WGA staining and TUNEL assay, respectively. The 4E-binding protein 1 (4E-BP1) and ribosomal S6 (S6) in myocardium were determined by western blot. mTOR-Raptor association was tested by co-immunoprecipitation assay in H9C2 cell line. Treatment with cardamonin, MI mice displayed that heart hypertrophy and heart dysfunction were alleviated, and cardiac fibrosis, cardiomyocyte size and cell apoptosis of border area were decreased (P<0.05). Besides, cardamonin can inhibit 4E-BP1 and S6 phosphorylation in heart of MI mice and H9C2 cell line (P<0.05). Furthermore, cardamonin disrupted mTOR-Raptor association in vitro. Cardamonin exerted cardio-protection against ALVR through mTORC1 inhibition.