1. Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan;
2. Department of Obstetrics and Gynecology, Taichung Veteran's General Hospital, Taichung 40705,Taiwan;
3. Department of Nursing, MeiHo University, Pingtung 91202, Taiwan;
4. Section of Cardiology, Yuan Rung Hospital, Yuanlin, Taiwan;
5. 5Institute of Oral Sciences, College of Oral Medicine, Chung Shan Medical University, Taichung40201, Taiwan;
6. Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan;
7. School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan;
8. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei11031, Taiwan;
9. Department of Biotechnology, Bharathiar University, Coimbatore-641 046, India;
10. Department of Biological Science and Technology, China Medical University, Taichung 40402,Taiwan;
11. Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan;
12. School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
Cardiomyopathy involves changes in the myocardial ultra-structure, hypertrophy, apoptosis, fibrosis and inflammation. Angiotensin II (AngII) stimulates the expression of insulin like-growth factors (IGF-2) and IGF-2 receptor (IGF-2R) in H9c2 cardiomyoblasts and subsequently leads to apoptosis. Estrogen receptors protect cardiomyocytes from apoptosis and fibrosis. Tanshinone IIA (TSN), a main active ingredient from Danshen, has been shown to protect cardiomyocytes from death caused by different stress signals. Estrogen receptor α (ER) is required for the rapid activation of the IGF-1R signaling cascade. This study aimed to investigate whether TSN protected H9c2 cardiomyocytes from AngII-induced activation of IGF-2R pathway and hypertrophy via ERs. We found that AngII caused the reduction in IGF-1R phosphorylation and the elevation of β-catenin and IGF-2R levels. This was reversed by increasing doses of TSN and of caspase-3 and ERK1/2 phosphorylation mediated by ERs. The phytoestrogen significantly attenuated AngII-induced apoptosis and suppressed the subsequent cardiac remodeling effect. Therefore, TSN reduced the AngII-induced activation of β-catenin and IGF-2R pathways, apoptosis and cardiac remodeling via ERs in H9c2 cardiomyoblasts.
Keywords: Angiotensin II, β-Catenin, Estrogen receptors, H9c2 Cardiomyoblasts, Insulin-like Growth Factor-2 Receptor, Tanshinone IIA.