Atorvastatin downregulates monocyte CD36 expression, nuclear NFkappaB and TNFalpha levels in type 2 diabetes

J Atheroscler Thromb. 2010 Jun 30;17(6):539-45. doi: 10.5551/jat.2956. Epub 2010 Feb 5.

Abstract

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 (NFkappaB) 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 choles-terol (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 NFkappaB levels (p<0.05). Finally, TNFalpha 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.

MeSH terms

  • Aged
  • Anticholesteremic Agents
  • Atorvastatin
  • CD36 Antigens / analysis*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Down-Regulation / drug effects
  • Female
  • Heptanoic Acids / pharmacology*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / prevention & control
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • NF-kappaB-Inducing Kinase
  • Protein Serine-Threonine Kinases / analysis*
  • Pyrroles / pharmacology*
  • Tumor Necrosis Factor-alpha / analysis*

Substances

  • Anticholesteremic Agents
  • CD36 Antigens
  • Heptanoic Acids
  • Pyrroles
  • Tumor Necrosis Factor-alpha
  • Atorvastatin
  • Protein Serine-Threonine Kinases