Histological analysis of defective colonic healing as a result of angiostatin treatment.
Antiangiogenic therapy is a highly promising new strategy in the treatment of cancer. One of the first angiogenesis inhibitors described was angiostatin, a 38-kDa internal proteolytically generated fragment of plasminogen. In a previous study we found that angiostatin affected physiological angiogenesis as well as tumor angiogenesis. It impaired healing when administered during repair of experimental colonic anastomoses, as reflected by a decrease in mechanical strength. On histology, we observed a decrease in factor VIII-stained vessel amount and volume in angiostatin-treated colonic anastomoses. The exact working mechanism of angiostatin has not been elucidated. Based on the available studies on proposed working mechanisms of angiostatin, we have attempted to address histological differences in physiological angiogenesis between the tissues of colonic anastomoses of mice with impaired healing and control mice. After angiostatin treatment there was more inflammatory tissue as a result of impaired healing. Furthermore, we found fewer vessels in the granulation tissue after angiostatin treatment. However, especially with respect to extracellular matrix (ECM), endothelial cell apoptosis, proliferation, or neutrophil influx, no gross differences were discerned 1 week following surgery, using histology and immunohistochemistry techniques.
D000714:Anastomosis, Surgical; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D043168:Angiostatins; D000818:Animals; D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D003106:Colon / Q000098:blood supply / Q000293:injuries*; D004730:Endothelium, Vascular / Q000473:pathology; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology; D010446:Peptide Fragments / Q000627:therapeutic use*; D010958:Plasminogen / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology*; D000099216:Chondroitin Sulfate Proteoglycan 4
D020533:Angiogenesis Inhibitors; D043168:Angiostatins; D000941:Antigens; D010446:Peptide Fragments; D010958:Plasminogen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D040301:Vascular Endothelial Growth Factor Receptor-2; D000099216:Chondroitin Sulfate Proteoglycan 4