Advanced glycation end products (AGE) enhance vascular endothelial growth factor (VEGF) production in promonocytic leukaemia THP-1 cells
Pertńaska-Marczewska M., Feldmann M., Paleolog EM.
It is becoming apparent that diabetes results in the increased expression of angiogenic growth factors in numerous tissues as a response to both hyperglycemia and tissue ischemic. Angiogenesis is regulated by vascular growth factor, particularly the vascular endothelial growth family of proteins (VEGF). Glucose binds to protein amino residues and forms early glycation products such as Schiff base and Amadori products. The final Maillard reaction leading to the production of advanced glycation end products (AGE) is slow, irreversible and dependent on plasma glucose concentration. AGE are now thought to contribute to the development of chronic vascular dysfunction, including the complications of diabetes. Although the mechanisms leading to the vascular complications of diabetes are not fully understood, AGE formation might be one of the answers. Aim: To determine VEGF production in THP-1 cells stimulated with glycated BSA and HSA, using different methods of glycation in vitro. Methods: BSA or HSA were incubated with D-glucose in PBS or sodium phosphate buffer at 37°C (150mM), at different time points; subsequently THP-1 cells were stimulated for 24 hours. Results: We observed strong induction of VEGF in supernatants from THP-1 cells stimulated with glycated HSA (1.67M glucose in 150mM NaH 2PO 4, pH 7.4 for 60 days) when compared to HSA without glucose. Glycated BSA induced strongest VEGF production with 6 weeks and 8 weeks samples versus non-glycated controls. Conclusions: Our results suggest an important role for AGE in stimulation of the development of angiogenesis observed in diabetic complications.