Background. Recent experimental studies have suggested a relevant contribution of lipid abnormalities in the development of the glomerulosclerosis associated with NIDDM-related nephropathy. Furthermore, clinical studies have recently suggested that HMG-CoA reductase inhibitors reduce proteinuria in diabetic population. However, it remains unclear how lipids cause glomerulosclerosis. The aim of this study was to assess whether primary lipid correction diminishes glomerulosclerosis and to characterize the mechanisms involved.Methods. Obese Zucker rats were used as a model of early diabetic nephropathy. Histological (desmin, chemokines, ED1, Ki67), biochemical and molecular analysis (TGF-b1 and PDGF-B) were performed to characterize the glomerular lesions. The high-tissue affinity ACE inhibitor quinapril was selected as a positive control of treatmentResults. Multivariate regression analysis showed that lesions in OZR may have been produced mainly by cholesterol. The lesions showed positive desmin staining in podocytes and weak cytokine expression. ACE inhibition normalized proteinuria, glomerular lesions and desmin staining in podocytes. HMG-CoA inhibition with atorvastatin ameliorated renal damage and proteinuria, and was independently associated with high cholesterol levels. Conclusions. Renal lesions in OZR were correlated with high blood cholesterol levels, proteinuria and glomerular damage. Atorvastatin decreased proteinuria and preserved podocyte injury, probably due to the improvement on blood lipids as well as to its non-lipid effects. As expected, quinapril exerted a more marked beneficial effect on those parameters. Treatment with ACE inhibitors and statins could be relevant for the treatment of diabetic nephropathy in humans.Key words: cholesterol, atorvastatin, podocyte, Zucker obese, quinapril.
| Identifer | oai:union.ndltd.org:TDX_UAB/oai:www.tdx.cat:10803/4391 |
| Date | 29 January 2002 |
| Creators | Blanco Cano, Sandra |
| Contributors | Romero, Ramón, Pujol-Borrell, Ricardo, Universitat Autònoma de Barcelona. Departament de Medicina |
| Publisher | Universitat Autònoma de Barcelona |
| Source Sets | Universitat Autònoma de Barcelona |
| Language | Spanish |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Source | TDX (Tesis Doctorals en Xarxa) |
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