In vitro angiomodulatory activity of sera from type 2 diabetic patients with background retinopathy

Abstract

Diabetic retinopathy is the leading cause of adult vision loss and blindness. The most important contributors to the development of diabetic retinopathy are hyperglycemia and hypoxemia that lead to increased vasopermeability, endothelial cell proliferation, and pathological neovascularization. In our previous studies, close relationship between proangiogenic activity of sera from type 2 diabetes mellitus patients (DM2) with background retinopathy, assessed in the in vivo serum-induced mouse cutaneous test (SIA), and VEGF and IL-18 serum concentration were observed. Moreover, it was clearly shown that IGF-1 might play an important role in the negative regulation of neoangiogenesis induced by DM2 patients' sera by diminishing the VEGF stimulatory effect. To confirm the observed phenomenon we evaluated the effect of DM2 patients' sera on the in vitro proliferative activity of human endothelial cells, which is critical for the sprouting and generation of new blood capillaries. Endothelial proliferative activity was significantly higher in the presence of sera from DM2 patients than from healthy controls (P<0.001), as estimated by the MTT test. Moreover, the examined sera from DM2 patients were characterized by increased IL-18 (P<0.05), diminished IGF-1 (P<0.02), and unchanged VEGF levels compared with those in controls. In conclusion, the present study showed a strong stimulatory effect of DM2 patients' sera on the proliferation of endothelial cells, which, along with the findings of our previous studies, proves that the described phenomenon is universal and valid for both animal and human endothelium.