Lipopolysaccharide-Induced VEGF Production and Ambient Oxidative Stress in Type 2 Diabetes

Abstract

Context: Oxidative stress is implicated in the development of vascular disease and is associated with an upregulation of vascular endothelial growth factor (VEGF), which is pathogenetically linked to the microvascular complications of diabetes. Patients of African origin have an increased susceptibility to microvascular kidney disease compared with white patients; the reasons and mechanisms that contribute to this vulnerability are unclear. Objectives: To investigate whether there are ethnic differences in lipopolysaccharide-induced monocyte VEGF production in whole blood cell cultures. In addition, to assess whether stimulated VEGF production is related to prevailing oxidative stress assessed by plasma lipid hydroperoxides (LOOHs) and α-tocopherol. Design and Setting: Cross-sectional study at a secondary care center in North London, United Kingdom, serving an inner-city community of 154,000 adults. Patients: African-Caribbean and white patients with type 2 diabetes mellitus [(T2DM); n = 52]. Results: Lipopolysaccharide-induced production of VEGF in whole blood cultures [61.8 (31.9) pg/mL to 78.4 (6.0) pg/mL; P < 0.001] correlated positively with LOOH levels (r = 0.3, P = 0.04) and was significantly higher in African-Caribbean than white patients with T2DM [404 (207.5) vs 268.8 (137.0)] pg/mL ×109/L monocytes; P = 0.018]. Plasma α-tocopherol concentration was higher in Caucasian (white) patients [40.3 (18.3) vs 30.0 (9.6)] μmol/L; P = 0.04] compared with African-Caribbean patients. Conclusions: This study suggests that the redox environment influences VEGF production in response to proinflammatory stimuli in T2DM. The differential responsiveness by ethnic origin may be of relevance in the variations in susceptibility to the long-term microvascular complications.