Abstract
Background: It has been reported that epilepsy leads to cardiac injury, but the underlying mechanisms have not yet been elucidated. Studies indicated that the calcium-sensing receptor (CaSR) is involved in cardiomyocyte apoptosis. However, the role of CaSR in epilepsy-induced cardiac injury remains unclear. Objective: The aim of this study was to investigate the effects of CaSR on cardiac injury of hereditary epileptic rats. Methods: The tremor (TRM) rat was used as an epilepsy model. Apoptotic rate, collagen volume fraction, and the expression of CaSR, Bcl-2, Bax, caspase-3, extracellular signal-regulated protein kinase (ERK), c-Jun NH<sub>2</sub>-terminal protein kinase (JNK), p38 mitogen-activated protein kinase (MAPK), transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>), connective tissue growth factor (CTGF), collagen I and collagen III protein were analyzed. Results: The results showed that the CaSR protein was increased in TRM rat hearts. Cardiac apoptosis and fibrosis were also observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Masson's trichrome staining, respectively. Further results demonstrated that the expression of Bax, caspase-3, P-JNK, P-p38, TGF-β<sub>1</sub>, CTGF, collagen I and collagen III protein were upregulated, whereas Bcl-2 and P-ERK were downregulated in TRM rat hearts. Moreover, these deleterious changes were further aggravated by GdCl<sub>3</sub> and attenuated by NPS-2390. Conclusions: Our results suggest that CaSR promotes cardiac apoptosis and fibrosis in TRM rat through the induction of mitochondrial and MAPK pathways as well as the activation of TGF-β<sub>1</sub> and CTGF.
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