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


CONCLUSIONS
These results suggest that atorvastatin therapy, beside lowering serum cholesterol levels, could exert anti-atherogenic and anti-inflammatory effects in type 2 diabetic patients.
Department of Clinical Sciences, Sapienza University of Rome, Rome, Italy.
Elisabetta
E
Mandosi
Mara
M
Fallarino
Alessandra
A
Gatti
Anna
A
Carnovale
Marco
M
Rossetti
Emanuela
E
Lococo
Barbara
B
Buchetti
Sebastiano
S
Filetti
Luisa
L
Lenti
Susanna
S
Morano
D000368:Aged; D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D018955:CD36 Antigens / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis*; D011758:Pyrroles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D000097782:NF-kappaB-Inducing Kinase
D000924:Anticholesteremic Agents; D000069059:Atorvastatin; D018955:CD36 Antigens; D006538:Heptanoic Acids; D017346:Protein Serine-Threonine Kinases; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase