Blockade of KCa3.1 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction

Chen-Hui Ju, Xian-Pei Wang, Chuan-Yu Gao, Shuang-Xia Zhang, Xing-Hua Ma, Chang Liu
Cellular Physiology and Biochemistry 2015, 36 (4): 1305-15

BACKGROUND/AIMS: After myocardial infarction (MI), cardiac fibrosis greatly contributes to left ventricular remodeling and heart failure. The intermediate-conductance calcium-activated potassium Channel (KCa3.1) has been recently proposed as an attractive target of fibrosis. The present study aimed to detect the effects of KCa3.1 blockade on ventricular remodeling following MI and its potential mechanisms.

METHODS: Myocardial expression of KCa3.1 was initially measured in a mouse MI model by Western blot and real time-polymerase chain reaction. Then after treatment with TRAM-34, a highly selective KCa3.1 blocker, heart function and fibrosis were evaluated by echocardiography, histology and immunohistochemistry. Furthermore, the role of KCa3.1 in neonatal mouse cardiac fibroblasts (CFs) stimulated by angiotensin II (Ang II) was tested.

RESULTS: Myocardium expressed high level of KCa3.1 after MI. Pharmacological blockade of KCa3.1 channel improved heart function and reduced ventricular dilation and fibrosis. Besides, a lower prevalence of myofibroblasts was found in TRAM-34 treatment group. In vitro studies KCa3.1 was up regulated in CFs induced by Ang II and suppressed by its blocker.KCa3.1 pharmacological blockade attenuated CFs proliferation, differentiation and profibrogenic genes expression and may regulating through AKT and ERK1/2 pathways.

CONCLUSION: Blockade of KCa3.1 is able to attenuate ventricular remodeling after MI through inhibiting the pro-fibrotic effects of CFs.

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