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- Title
Catalase overexpression prevents hypertension and tubular apoptosis in angiotensinogen transgenic mice.
- Authors
Godin, Nicolas; Fang Liu; Lau, Garnet J.; Brezniceanu, Marie-Luise; Chénier, Isabelle; Filep, Janos G.; Ingelfinger, Julie R.; Shao-Ling Zhang; Chan, John S. D.
- Abstract
Transgenic mice that overexpress angiotensinogen, the sole precursor of angiotensins, in their renal proximal tubular cells develop hypertension, albuminuria, and tubular apoptosis. These pathological changes are due to enhanced generation of reactive oxygen species in the proximal tubule cells. Here, we determined whether overexpression of catalase to decrease oxidant injury in the proximal tubular cells could reverse these abnormalities. Double-transgenic mice specifically overexpressing angiotensinogen and catalase in their renal proximal tubular cells were created by cross-breeding the single transgenics. Non-transgenic littermates served as controls. Overexpression of catalase prevented hypertension, albuminuria, tubulointerstitial fibrosis, and tubular apoptosis in the angiotensinogen transgenic mice. Furthermore, the double transgenics had lower reactive oxygen species generation and reduced pro-fibrotic and apoptotic gene expression in the renal proximal tubular cells. Renal angiotensin converting enzyme-2 expression and urinary angiotensin 1–7 levels were downregulated in the single but normal in the double-transgenic mice. Thus, we suggest that the intrarenal renin-angiotensin system and reactive oxygen species generation have an important role in the development of hypertension and renal injury.
- Subjects
TRANSGENIC mice; CATALASE; CARDIOVASCULAR disease prevention; HYPERTENSION; ALBUMINURIA; APOPTOSIS prevention
- Publication
Kidney International, 2010, Vol 77, Issue 12, p1086
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2010.63