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 AF.