Mesenchymal Stem Cells (MSC) Prevented the Progression of Renovascular Hypertension, Improved Renal Function and Architecture

Mesenchymal Stem Cells (MSC) Prevented the Progression of Renovascular Hypertension, Improved Renal Function and Architecture

Author Oliveira-Sales, Elizabeth Barbosa de Autor UNIFESP Google Scholar
Maquigussa, Edgar Autor UNIFESP Google Scholar
Semedo, Patricia Autor UNIFESP Google Scholar
Pereira, Luciana G. Autor UNIFESP Google Scholar
Ferreira, Vanessa M. Autor UNIFESP Google Scholar
Câmara, Niels Olsen Saraiva Autor UNIFESP Google Scholar
Bergamaschi, Cassia Toledo Autor UNIFESP Google Scholar
Campos, Ruy Ribeiro Autor UNIFESP Google Scholar
Boim, Mirian Aparecida Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract Renovascular hypertension induced by 2 Kidney-1 Clip (2K-1C) is a renin-angiotensin-system (RAS)-dependent model, leading to renal vascular rarefaction and renal failure. RAS inhibitors are not able to reduce arterial pressure (AP) and/or preserve the renal function, and thus, alternative therapies are needed. Three weeks after left renal artery occlusion, fluorescently tagged mesenchymal stem cells (MSC) (2x10(5) cells/animal) were injected weekly into the tail vein in 2K-1C hypertensive rats. Flow cytometry showed labeled MSC in the cortex and medulla of the clipped kidney. MSC prevented a further increase in the AP, significantly reduced proteinuria and decreased sympathetic hyperactivity in 2K-1C rats. Renal function parameters were unchanged, except for an increase in urinary volume observed in 2K-1C rats, which was not corrected by MSC. the treatment improved the morphology and decreased the fibrotic areas in the clipped kidney and also significantly reduced renal vascular rarefaction typical of 2K-1C model. Expression levels of IL-1 beta, TNF-alpha angiotensinogen, ACE, and Ang II receptor AT(1) were elevated, whereas AT(2) levels were decreased in the medulla of the clipped kidney. MSC normalized these expression levels. in conclusion, MSC therapy in the 2K-1C model (i) prevented the progressive increase of AP, (ii) improved renal morphology and microvascular rarefaction, (iii) reduced fibrosis, proteinuria and inflammatory cytokines, (iv) suppressed the intrarenal RAS, iv) decreased sympathetic hyperactivity in anesthetized animals and v) MSC were detected at the CNS suggesting that the cells crossed the blood-brain barrier. This therapy may be a promising strategy to treat renovascular hypertension and its renal consequences in the near future.
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Date 2013-11-04
Published in Plos One. San Francisco: Public Library Science, v. 8, n. 11, 10 p., 2013.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 10
Origin http://dx.doi.org/10.1371/journal.pone.0078464
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000326503400064
URI http://repositorio.unifesp.br/handle/11600/36971

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