Transmyocardial laser revascularization induced angiogenesis correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor.

Abstract

Transmyocardial laser revascularization (TMLR) has been widely evaluated as a treatment for ischemic myocardium. However, its mechanism remains unclear. One mechanism is angiogenesis. This study examines the relationship between TMLR and angiogenesis from the viewpoint of matrix metalloproteinases and platelet-derived endothelial cell growth factor. The left anterior descending coronary artery (LAD) was ligated permanently in 12 beagle dogs. TMLR was accomplished in six of the 12 dogs using a carbon dioxide laser. No laser treatment was done in the six control dogs. Two weeks after the initial operation, dogs were euthanized and transmural samples (each of approximately 0.5 g) were cut from the center of the infarcted LAD territory, right ventricular wall, left circumflex artery perfuse area and interventricular septum except the LAD perfuse area. They were snap-frozen in liquid nitrogen for matrix metalloproteinases and platelet-derived endothelial cell growth factor activity analysis. Hematoxylin and eosin staining, double immunohistologic staining with anti-proliferating cell nuclear antigen and von Willebrand factor antibody, and immunohistologic staining with antibody against platelet-derived endothelial cell growth factor were performed for histologic studies. The activities of matrix metalloproteinases were examined by gelatin zymography. The activity of platelet-derived endothelial cell growth factor was examined by a spectrophotometric method. The channels were found to be infiltrated with granulation tissue and fibrosis. In the laser group, the active matrix metalloproteinase-2 and platelet-derived endothelial cell growth factor activity in the area of the left anterior descending coronary artery was significantly higher than in the control group (P<0.0001 and P=0.037, respectively). Within the channel remnants or close to these areas, the number of von Willebrand factor positive microvessels and proliferating cell nuclear antigen with correlating von Willebrand factor positive microvessels were significantly higher than in the control group (P=0.001 and P=0.0006, respectively). These increases in microvessels significantly correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor. Based on these findings it was concluded that transmyocardial laser revascularization induced angiogenesis correlated with the expression of active matrix metalloproteinases-2 and platelet-derived endothelial cell growth factor.