RGD Reference Report - Rosuvastatin treatment prevents progressive kidney inflammation and fibrosis in stroke-prone rats. - Rat Genome Database

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Rosuvastatin treatment prevents progressive kidney inflammation and fibrosis in stroke-prone rats.

Authors: Gianella, A  Nobili, E  Abbate, M  Zoja, C  Gelosa, P  Mussoni, L  Bellosta, S  Canavesi, M  Rottoli, D  Guerrini, U  Brioschi, M  Banfi, C  Tremoli, E  Remuzzi, G  Sironi, L 
Citation: Gianella A, etal., Am J Pathol. 2007 Apr;170(4):1165-77.
RGD ID: 1642041
Pubmed: PMID:17392157   (View Abstract at PubMed)
PMCID: PMC1829451   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.060882   (Journal Full-text)

Salt-loaded, spontaneously hypertensive stroke-prone rats show progressive increases in blood pressure and proteinuria and accumulate acute-phase proteins in body fluids, modeling events during renal damage. The aim of this study was to assess the pathological events occurring in the kidney of spontaneously hypertensive stroke-prone rats over time and evaluate the effects of statin treatment, which is known to improve renal and cardiovascular outcomes. Kidneys of male spontaneously hypertensive stroke-prone rats 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 characterized by the increased renal expression of plasminogen activator inhibitor-1, tissue plasminogen activator, and urokinase plasminogen activator; the net result was an increase in plasmin and matrix metalloproteinase (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. These data suggest that rosuvastatin may have potential utility as a therapeutic option in renal diseases that are characterized by inflammation and fibrosis.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
MMP9Humankidney disease  ISOMmp9 (Rattus norvegicus)protein:decreased expression:kidneyRGD 
Mmp9Ratkidney disease  IEP protein:decreased expression:kidneyRGD 
Mmp9Mousekidney disease  ISOMmp9 (Rattus norvegicus)protein:decreased expression:kidneyRGD 


Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)