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ROSUVASTATIN EXERTS RENOPROTECTIVE EFFECTS IN STROKE-PRONE RATS BY MODULATING THE PLASMINOGEN/PLASMIN SYSTEM AND THE METALLOPROTEASES EXPRESSION
Abstract number: P-S-403
Nobili1 E., Gianella1 A., Gelosa1 P., Sironi1 L., Bellosta1 S., Canavesi1 M., Abbate2 M., Zoja2 C., Tremoli1 E., Mussoni1 L.
11Dept of Pharmacological Sciences, University of Milan, Milan 22Mario Negri Institute for Pharmacological Research, Mario Negri, Bergamo, Italy
How-to-cite Nobili E, Gianella A, Gelosa P, Sironi L, Bellosta S, Canavesi M, Abbate M, Zoja C, Tremoli E, Mussoni L. ROSUVASTATIN EXERTS RENOPROTECTIVE EFFECTS IN STROKE-PRONE RATS BY MODULATING THE PLASMINOGEN/PLASMIN SYSTEM AND THE METALLOPROTEASES EXPRESSION. J Thromb Haemost 2007; 5 Supplement 2: P-S-403
Abstract
Introduction: Salt-loaded spontaneously hypertensive, stroke-prone rats (SHRSP) show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modelling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of SHRSP over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes.
Methods: Fifty six-week-old SHRSPs were fed a high-salt diet and randomly divided into three groups for oral treatment with vehicle, rosuvastatin or simvastatin at the dose of 10 mg/kg/day (n=15 each group). Animals were euthanized at different time of proteinuria and the kidneys collected for histological evaluation and profile of the fibrinolytic and metalloprotease systems. For comparison, baseline kidneys from SHRSP (n=6) were collected at the start of the high-salt diet
Results: By electron microscopy, we observed that kidneys of male SHRSP euthanized at different stages of proteinuria showed progressive inflammatory cell infiltration, the accumulation of alpha-smooth muscle actin-positive cells, degenerative changes in podocytes, and severe fibrosis. These were accompanied by an imbalance in the plasminogen/plasmin and metalloprotease systems characterised by the increased renal expression of PAI-1, tPA and uPA; the net result was an increase in plasmin and MMP-2 and a reduction in MMP-9 activity. Chronic treatment with the hydrophilic rosuvastatin had renoprotective effects in terms of morphology and inflammation and prevented the changes in plasmin, MMP-2 and MMP-9 activity. These effects were independent of the changes in blood pressure and plasma lipid levels. Treatment with the lipophilic simvastatin was not renoprotective.
Conclusions: These data suggest that some statin with hydrophilic properties may have potential utility as a therapeutic option in renal diseases that are characterised by inflammation and fibrosis
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
Session Details
| Date: |
01/08/2007
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| Time: |
00:00-00:00
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| Session name: |
XXIst ISTH Congress |
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| Location: |
Oxford, UK |
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