Wound healing: a model for the study of diabetic angiopathy.

Wound healing as a model for diabetic angiopathy has been studied by light and electron microscopy. Biochemical studies of the rate of incorporation of 3H-proline and 3H-thymidine into collagen and DNA, respectively, have confirmed the morphologic observations. In both the normal and the diabetic, there was a marked decrease in the rate of collagen and DNA synthesis, suggesting that most of the cells in the biopsies were stunned by the injury and ceased DNA replication during the initial phase. In control mice this decrease was followed by a modest but significant burst of DNA replication, which peaked at two hours and by the fourth hour had returned to the one-hour level. In the diabetic this burst of DNA replication was absent and no capillary morphogenesis was seen at two, four, and eight hours. At 16 hours, there were only a few abnormal nascent vessels observed in the diabetic and antiserum-treated mice. The peak in the rate of collagen synthesis at four hours correlated well with the condensation of collagen at the wound margin and the fibroblast rough-endoplasmic-reticulum (RER) proliferation. In the diabetic mice, there was a significantly attenuated rate of collagen synthesis for the entire 16-hour period. The lack of DNA replication, capillary morphogenesis, fibroblast RER proliferation, and decreased collagen synthesis in the diabetic mouse can be considered interrelated and significant factors in the diabetic's impaired response to cellular injury. In view of the increased frequency and severity of injury to the circulation of the diabetic and the impaired response to repair such injury, it is likely that wound healing is a promising model for diabetic angiopathy.