Skip Navigation



NDT Advance Access published online on September 12, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl495
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
21/11/3087    most recent
gfl495v2
gfl495v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Smeets, B.
Right arrow Articles by Wetzels, J. F. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smeets, B.
Right arrow Articles by Wetzels, J. F. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 31, 2006
Accepted July 24, 2006

Original Article

Angiotensin converting enzyme inhibition prevents development of collapsing focal segmental glomerulosclersis in Thy-1.1 transgenic mice

Bart Smeets 1 *, Mark L. M. Steenbergen 1, Henry B. P. M. Dijkman 1, Kiek N. Verrijp 1, Nathalie A. J. M. te Loeke 1, Jan Aten 2, Eric J. Steenbergen 1, and Jack F. M. Wetzels 3

1 Department of Pathology, Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands
2 Department of Pathology, Academic Medical Center University Amsterdam, Amsterdam, the Netherlands
3 Department of Nephrology, Radboud University Medical Centre Nijmegen, Nijmegen, the Netherlands

* To whom correspondence should be addressed.
Bart Smeets, E-mail: b.smeets{at}pathol.umcn.nl



  Abstract

Background. Thy-1.1 transgenic mice develop hypercellular focal and segmental glomerulosclerosis (FSGS) lesions that mimic human collapsing FSGS, in 7 days after injection with anti-Thy-1.1 antibodies. These lesions consist of proliferating parietal epithelial cells (PECs). We questioned whether the angiotensin converting enzyme inhibitor (ACE), captopril, could prevent the development of FSGS and if protection is related to the timing of drug administration.

Methods. First, we compared the effect of captopril treatment with angiotensin II-(ANGII) independent antihypertensive therapy (triple therapy). Second, we tested the effects of captopril administered over four different time intervals: days -7 to 0 (Ca-7>0), days -7 to 7 (Ca-7>7), days 0-7 (Ca0>7) and days 3-7 (Ca3>7) (day 0 being the day of injection of the antibody).

Results. In anti-Thy-1.1 injected control (C) mice we observed dedifferentiation and activation of podocytes, reflected by loss of ASD33 and increased expression of desmin, followed by a marked accumulation of PECs forming hypercellular lesions. PECs showed an increased expression of connective tissue growth factor (CTGF). Triple therapy or captorpil pre-treatment (Ca-7>0) had no significant effect on albuminuria or FSGS. In contrast, Ca0>7 and Ca3>7 treatment significantly lowered albuminuria and attenuated development of FSGS. The latter two treatments attenuated loss of ASD33 expression by podocytes but could not prevent increased desmin expression. In addition, these treatments reduced CTGF expression by PECs and prevented PEC proliferation.

Conclusions. ACE inhibition, but not triple therapy, prevents the development of FSGS, suggesting an important role for ANGII. ACE inhibition has a protective effect even when started 3 days after the initial podocyte insult, which is probably related to the ability of ACE-inhibition to block PEC activation and proliferation.

Keywords: angiotensin converting enzyme; collapsing glomerulopathy; connective tissue growth factor; focal segmental glomerulosclerosis; parietal epithelial cell; podocyte.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.