Neuregulin-1 protects cardiac electrical conduction through downregulating matrix metalloproteinase-9 and upregulating connexin 43 in a rat myocardial infarction model.

Abstract

Aims: Neuregulin-1 (NRG-1) is a member of the epidermal growth factor family, and has an important role in cardiomyocyte development and myocardial regeneration. The aim of this study was to determine the protective effect of NRG-1 on cardiac electrical conduction in a rat myocardial infarction (MI) model. Methods: Thirty-three adult male SPF SD rats were randomized into three groups: sham-operated (n=9), acute myocardial infarction (AMI, n=12), and the NRG-1-treated (NRG-1, n=12) groups. All rats were sacrificed on day 8 after inducing MI. The 6-lead electrocardiograms (ECG) were recorded pre-operatively and eight days after operation, and analyzed. The expression levels of matrix metalloproteinase (MMP)-9 and gap junction protein connexin 43 (Cx43) in the infarcted myocardium were measured by Western blotting, and its in-situ distribution was evaluated using immunohistochemistry. Results: The PR, QRS and QT intervals were significantly prolonged in the AMI group compared to the sham operated animals (P<0.05, P<0.01 and P<0.01 respectively), and the PR and QRS intervals were partially restored in the NRG-1-treated rats (P<0.01 and P<0.01 compared to AMI group). Similarly, the increased levels of MMP-9 in the AMI group was restored upon NRG-1 treatment. The myocardial expression of Cx43 was decreased significantly in the AMI group, and was upregulated by NRG-1 treatment. Conclusions: NRG-1 attenuates MI-induced dysfunctional cardiac electrical conduction by downregulating MMP-9 and upregulating Cx43.