Artikel
Anti-Inflammatory properties of atorvastatin exert cardioprotective effects in experimental diabetic cardiopathy
Anti-inflammatorische Eigenschaften von Atorvastatin bewirken kardioprotektive Effekte bei der experimentellen diabetischen Kardiopathie
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Autoren
Veröffentlicht: | 11. November 2004 |
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Gliederung
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Background
Cardioprotective and small-GTP-binding protein (Rac1, RhoA)-dependent effects of statins could be involved in the interactions between cell adhesion molecules (CAMs) and may inhibit transendothelial migration of leukocytes. We investigated the potential anti-inflammatory effects of atorvastatin (ATOR), using a dose too low to affect the lipid profile, on the development of streptozotocin (STZ)-induced diabetic cardiopathy.
Methods and Results
ICAM, VCAM, iNOS, CD18+ leukocytes, TNFa, IL-1b, and collagen I and III content were visualized immunohistochemically and quantified by digital image analysis in heart cryosections in Sprague-Dawley (SD) and in vehicle- or ATOR-treated (50mg/kg/24h; p.o.) diabetic rats (SD-STZ; 6 weeks after STZ injection; n=9/group). LV Rac1 and RhoA activities were determined by pull down assays. Hemodynamics (LVP; dP/dt max/min) were measured in anaesthetized open-chest animals by a tip catheter. Plasma cholesterol and LDL levels were determined. SD-STZ and SD-STZ ATOR rats developed hyperlipidemia, which was not affected by ATOR. LV function of SD-STZ was impaired vs. controls (LVP: 58.3±2.1 vs. 88.2±4.5mmHg; dP/dtmax: 2800±280mmHg vs. 4600±320 mmHg/s; dP/dtmin: -2210±280 vs. -3972±340 mmHg/s). LV function of SD-STZ ATOR was improved by 27% vs. SD-STZ, which correlated with an increase in CAMs, CD18, cytokine and collagen expression [Tab. 1] and in increased RhoA (+70%) and Rac1 activities (+60%) (P<0.05) vs. controls. LV function of SD-STZ ATOR was improved by 27% vs. SD-STZ, and CAMs, cytokine and collagen expression were significant reduced vs. SD-STZ (P<0.05). LV RhoA and Rac1 activities did not differ compared to controls.
Conclusion
In experimental diabetic cardiopathy anti-inflammatory cardioprotective properties of statins are LDL independent and involves a reduction in RhoA and Rac1 activity.