Role of matrix metalloproteinase-7 and apoptosis-associated gene expression levels in the pathogenesis of atrial fibrosis in a Beagle dog model

Abstract

The aim of the present study was to investigate the potential role of matrix metalloproteinase-7 (MMP-7) and apoptosis-associated genes [TIMP metallopeptidase inhibitor 2(TIMP-2), BCL2 associated X, apoptosis regulator (BAX) and BCL2, apoptosis regulator (BCL-2)] in the pathogenesis of atrial fibrillation (AF) in a Beagle dog model. A total of 20 adult male Beagle dogs were randomly assigned into the AF group (n=10; Beagle dogs were treated by Burst stimulation to induce AF) and the control group (n=10; healthy Beagle dogs). Echocardiography and Mallory staining were used to determine cardiac function and degree of atrial fibrosis, respectively. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to determine collagen type 1 (Col I), MMP-7, TIMP-2, BAX and BCL-2 mRNA and protein expression levels. Compared with the control group, the AF group presented increased degree of atrial fibrosis and level of Col I expression, elevated MMP-7 and BAX expression levels, but decreased TIMP-2 and BCL-2 expression levels. Correlation analysis demonstrated that MMP-7 and BAX protein expression levels were negatively correlated with left ventricular ejection fraction (LVEF), but positively correlated with the degree of atrial fibrosis. Negative correlation was observed between TIMP-2 and BCL-2 protein expression levels and degree of atrial fibrosis. In addition, a positive correlation between TIMP-2 and BCL-2 protein expression levels and LEVF was observed. These results demonstrate that MMP-7 and BAX were highly expressed, while TIMP-2 and BCL-2 were downregulated in a Beagle dog model of AF, indicating that MMP-7 and apoptosis-associated genes (TIMP-2, BAX and BCL-2) may be associated with the pathogenesis of A F.