Rat cardiac fibroblasts inhibit gap junction between cardiomyocytes through increasing matrix metalloproteinase 2 activity.

AIM: To investigate the effect of conditioned medium from hypoxia/reoxygenation (H/R)-treated rat cardiac fibroblasts (CFs) on gap junction between cardiomyocytes and determine whether its mechanism is related to matrix metalloproteinase 2 (MMP2) activity. METHODS: (1) H9c2 cells were randomly divided into five groups: control group, normal group, ARP-100 group, H/R group, and H/R+ARP-100 group. Scrape loading/dye transfer assay was used to assess the gap junction function. Western blot was used to detect the expression and phosphorylation levels of Cx43. Gelatin zymography assay was performed to measure MMP2 activity. (2) SD rats were randomly divided into control group, ARP-100 group, ischemia-reperfusion (I/R) group, and I/R+ARP-100 group, with 8 rats in each group. Micro-electrode array technology was used to record the type and duration of arrhythmia. Immunohistochemistry experiment was performed to assess expression levels and distribution of Cx43 in myocardial tissues. RESULTS: Compared with the control group, the H/R group showed decreased protein expression of Cx43 (P<0. 01), narrowed distance of lucifer yellow diffusion (P<0. 01), and increased MMP2 activity (P<0. 01). ARP-100 attenuated H/R-induced gap junction dysfunction (P<0. 05). The arrhythmia score was also reduced after perfusion with ARP-100 (P<0. 01). CONCLUSION: H/R-treated rat CFs can inhibit gap junction between cardiomyocytes, and its mechanism may involve increased MMP2 activity. [ABSTRACT FROM AUTHOR]