Spatiotemporal induction of matrix metalloproteinase-9 transcription after discrete myocardial injury

摘要: Radiofrequency (RF) ablation of the myocardium causes discrete sites injury. RF scars can expand, altering extracellular matrix (ECM) structure and continuity electrical syncytium adjacent myocardium. Matrix metalloproteinases (MMPs), such as MMP-9, contribute to ECM remodeling. However, whether what degree transcriptional induction MMP-9 occurs after myocardial injury association with conduction patterns remains unexplored. This study examined gene promoter (M9PROM) activation using mice in which M9PROM was fused a β-galactosidase (β-gal) reporter. lesions (0.5-mm probe, 80°C, 30 s) were created on left ventricular (LV) epicardium (n=62) terminally studied at 1 h, d, 3 7 14 28 d localized through β-gal staining. The scar area staining measured normalized LV (planimetry). size increased from h post-RF-injury values by remained higher d. became evident peaked Electrical (potentiometric dye mapping) Heterogeneities action potentials impulse propagation coincident observed For example, proximal site slower than that remote (0.15±0.02 vs. 0.83±0.08 mm/ms, P<0.05). Thus, unique spatiotemporal pattern occurred injury, associated development heterogeneity. Therefore, these findings suggest changes key determinant remodeling, addition structure, arrhythmogenesis around region injury.—Mukherjee, R., Colbath, G. P., Justus, C. D., Bruce, J. A., Allen, M., Hewett, K. W., Saul, Gourdie, R. G., Spinale, F. Spatiotemporal metalloproteinase-9 transcription following