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

Objective: Transmyocardial laser revascularization (TMLR) has been widely e valuated as a treatment for ischemic myocardium. However, its mechanism rem ains unclear. One mechanism is angiogenesis. This study examines the relati onship between TMLR and angiogenesis from the viewpoint of matrix metallopr oteinases and platelet-derived endothelial cell growth factor. Methods: 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 wee ks after the initial operation, dogs were euthanized and transmural samples (each of approximately 0.5 g) were cut from the center of the infarcted LA D territory, right ventricular wall, left circumflex artery perfuse area an d interventricular septum except the LAD perfuse area. They were snap-froze n in Liquid nitrogen for matrix metalloproteinases and platelet-derived end othelial cell growth factor activity analysis. Hematoxylin and eosin staini ng, double immunohistologic staining with anti-proliferating cell nuclear a ntigen and von Willebrand factor antibody, and immunohistologic staining wi th antibody against platelet-derived endothelial cell growth factor were pe rformed for histologic studies. The activities of matrix metalloproteinases were examined by gelatin zymography. The activity of platelet-derived endo thelial cell growth factor was examined by a spectrophotometric method. Res ults: The channels were found to be infiltrated with granulation tissue and fibrosis. In the laser group, the active matrix metalloproteinase-2 and pl atelet-derived endothelial cell growth factor activity in the area of the l eft anterior descending coronary artery was significantly higher than in th e control group (P < 0.0001 and P = 0.037, respectively). Within the channe l remnants or close to these areas, the number of von Willebrand factor pos itive 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 increa ses in microvessels significantly correlated with the expression of matrix metalloproteinases and platelet-derived endothelial cell growth factor. Con clusion: Based on these findings it was concluded that transmyocardial lase r revascularization induced angiogenesis correlated with the expression of active matrix metalloproteinases-2 and platelet-derived endothelial cell gr owth factor. (C) 2001 Published by Elsevier Science B.V.