Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Medical management of diabetic retinopathy: fenofibrate and ACCORD Eye studies

The approach of all ophthalmologists, diabetologists and general practitioners seeing patients with diabetic retinopathy should be that good control of blood glucose, blood pressure and plasma lipids are all essential components of modern medical management. The more recent data on the use of fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye studies is reviewed. In FIELD, fenofibrate (200 mg/day) reduced the requirements for laser therapy and prevented disease progression in patients with pre-existing diabetic retinopathy. In ACCORD Eye, fenofibrate (160 mg daily) with simvastatin resulted in a 40% reduction in the odds of retinopathy progressing over 4 years, compared with simvastatin alone. This occurred with an increase in HDL-cholesterol and a decrease in the serum triglyceride level in the fenofibrate group, as compared with the placebo group, and was independent of glycaemic control. We believe fenofibrate is effective in preventing progression of established diabetic retinopathy in type 2 diabetes and should be considered for patients with pre-proliferative diabetic retinopathy and/or diabetic maculopathy, particularly in those with macular oedema requiring laser