Statin Treatment Reduces Inflammatory Markers and Improves Endothelial Function in Diabetic Rats
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- Category: Vol. 79, September 2011
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Statin Treatment Reduces Inflammatory Markers and Improves Endothelial Function in Diabetic Rats ALI F.I. ABDEL-WAHAB, M.D. and NAHED ABDEL-GHANI, M.D.
Abstract
Background: Endothelial dysfunction underlies cardio-vascular complications of diabetes that are responsible for increased morbidity and mortality. Treatment with HMG-CoA reductase inhibitors has been accompanied by a reduced risk of cardiovascular events.
Objective: To assess the effects of treatment with statins on levels of inflammatory biomarkers (hsCRP, neopterin & TNF-a) in experimental diabetes and to correlate these effects with vascular reactivity of isolated aortic strips, in presence and absence of the NOS inhibitor, L-NAME.
Methods: Rats, rendered diabetic by single injection of streptozotocin, were divided into 5 groups to receive either; saline, atorvastatin 4mg/kg/day, atorvastatin + LNAME 2mg/kg/day, rosuvastatin 2mg/kg/day, or rosuvastatin + LNAME; for 4 weeks, in addition to a group of non-diabetic control rats. At end of study, blood samples were collected for determination of blood levels of glucose, HbA(1c), total cholesterol, HDL-C, LDL-C, TGs and the inflammatory biomarkers (hsCRP, neopterin & TNF-a). Then aortae were isolated to study their responsiveness to phenylephrine (PE) and acetylcholine (ACh).
Abbreviations:
HMG-CoA reductase: 3-hydroxy-3methylglutaryl-co-enzyme A reductase.
HbA(1 c) : Glycosylated hemoglobin. TC : Total Cholesterol.
HDL-C : High Density lipoprotein. LDL-C : Low Density lipoprotein.
TGs : Triglycerides.
STZ : Streptozotocin.
PE : Phenylephrine.
ACh : Acetylcholine.
NOS : Nitic oxide synthase.
L-NAME : NG-nitro-L-arginine methyl ester. hsCRP : High-sensitivity C-reactive protein. TNF-a : Tumour necrosis factor alpha.
ED : Endothelial dysfunction.
Results: Treatment with the statins, atorvastatin and rosuvastatin, produced significant reductions in the blood lipid levels (LDL-C, TC & TGs) in diabetic rats. Statins also significantly reduced the elevated levels of inflammatory biomarkers (hsCRP, neopterin & TNF-a) in diabetic rats and these effects were not changed by the addition of L-NAME. The isolated aortic strips in diabetic rats showed significantly increased contractile response to PE and abolished vasorelaxant response to ACh compared with non-diabetic rats. Both exaggerated vascular contractility and inhibited relaxation responses were significantly improved in diabetic rats treated with statins, atorvastatin and rosuvastatin. Addition of L-NAME prevented the statin-induced beneficial effect on endothelial function despite maintained lipid lowering and decreased levels of inflammation markers.
Conclusion: Statin treatment is effective in reducing inflammatory markers and improving endothelial dysfunction associated with diabetes. This beneficial effect may be related to anti-inflammatory activity and enhanced NO synthesis. Thus, statin therapy is a useful preventive strategy in high risk diabetic patients to reduce LDL-cholesterol level, decrease inflammatory markers and improve endothelial function.