Atorvastatin Downregulates Monocyte CD36 Expression, Nuclear NF kappa B and TNF alpha Levels in Type 2 Diabetes

Aim: Type 2 diabetes increases the risk for cardiovascular disease, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) reduce cardiovascular events in these patients. The benefits of statin therapy cannot be explained only by the lipid-lowering effect. The aim of this study was to test the effect of atorvastatin therapy on CD36 scavenger receptor expression, nuclear factor-kappaB (NF kappa B) levels and markers of inflammation (C-reactive protein, CRP, Tumor Necrosis Factor-alpha, TNF-alpha) in circulating monocytes from diabetic patients. Methods: Twenty-two type 2 diabetic patients were treated for 8 weeks with atorvastatin (20 mg/day). At baseline and after treatment a blood sample was collected for measurement of glucose, lipid profile (total cholesterol, HDL, LDL cholesterol, triglycerides), glycated hemoglobin (HbA1c), CRP and for isolation of monocytes. Results: Atorvastatin decreased total (p<0.0001) and LDL (p<0.01), and incresased HDL cholesterol (p<0.02). CD36 surface protein expression (anti-CD36 fluorescein isothiocyanate-FITC) was reduced in circulating monocytes after atorvastatin therapy (p<0.02) while immunoblot analysis showed reduced nuclear and increased cytoplasm NF alpha B levels (p<0.05). Finally, TNF alpha production in lipopolysaccharide-activated monocytes from patients treated with atorvastatin was reduced (p<0.05). Conclusion: These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.