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Tipping the balance from angiogenesis to fibrosis in CKD

Chronic progressive renal fibrosis leads to end-stage renal failure many patients with chronic kidney disease (CKD). Loss of the rich peritubular capillary network is a prominent feature, and seems independent of the specific underlying disease. The mechanisms that contribute to peritubular capillar...

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Autores principales: Ballermann, Barbara J, Obeidat, Marya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536966/
https://www.ncbi.nlm.nih.gov/pubmed/26312149
http://dx.doi.org/10.1038/kisup.2014.9
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author Ballermann, Barbara J
Obeidat, Marya
author_facet Ballermann, Barbara J
Obeidat, Marya
author_sort Ballermann, Barbara J
collection PubMed
description Chronic progressive renal fibrosis leads to end-stage renal failure many patients with chronic kidney disease (CKD). Loss of the rich peritubular capillary network is a prominent feature, and seems independent of the specific underlying disease. The mechanisms that contribute to peritubular capillary regression include the loss of glomerular perfusion, as flow-dependent shear forces are required to provide the survival signal for endothelial cells. Also, reduced endothelial cell survival signals from sclerotic glomeruli and atrophic or injured tubule epithelial cells contribute to peritubular capillary regression. In response to direct tubular epithelial cell injury, and the inflammatory reaction that ensues, capillary pericytes dissociate from their blood vessels, also reducing endothelial cell survival. In addition, direct inflammatory injury of capillary endothelial cells, for instance in chronic allograft nephropathy, also contributes to capillary dropout. Chronic tissue hypoxia, which ensues from the rarefaction of the peritubular capillary network, can generate both an angiogenic and a fibrogenic response. However, in CKD, the balance is strongly tipped toward fibrogenesis. Understanding the underlying mechanisms for failed angiogenesis in CKD and harnessing endothelial-specific survival and pro-angiogenic mechanisms for therapy should be our goal if we are to reduce the disease burden from CKD.
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spelling pubmed-45369662015-08-24 Tipping the balance from angiogenesis to fibrosis in CKD Ballermann, Barbara J Obeidat, Marya Kidney Int Suppl (2011) Mini Review Chronic progressive renal fibrosis leads to end-stage renal failure many patients with chronic kidney disease (CKD). Loss of the rich peritubular capillary network is a prominent feature, and seems independent of the specific underlying disease. The mechanisms that contribute to peritubular capillary regression include the loss of glomerular perfusion, as flow-dependent shear forces are required to provide the survival signal for endothelial cells. Also, reduced endothelial cell survival signals from sclerotic glomeruli and atrophic or injured tubule epithelial cells contribute to peritubular capillary regression. In response to direct tubular epithelial cell injury, and the inflammatory reaction that ensues, capillary pericytes dissociate from their blood vessels, also reducing endothelial cell survival. In addition, direct inflammatory injury of capillary endothelial cells, for instance in chronic allograft nephropathy, also contributes to capillary dropout. Chronic tissue hypoxia, which ensues from the rarefaction of the peritubular capillary network, can generate both an angiogenic and a fibrogenic response. However, in CKD, the balance is strongly tipped toward fibrogenesis. Understanding the underlying mechanisms for failed angiogenesis in CKD and harnessing endothelial-specific survival and pro-angiogenic mechanisms for therapy should be our goal if we are to reduce the disease burden from CKD. Nature Publishing Group 2014-11 2014-10-31 /pmc/articles/PMC4536966/ /pubmed/26312149 http://dx.doi.org/10.1038/kisup.2014.9 Text en Copyright © 2014 International Society of Nephrology
spellingShingle Mini Review
Ballermann, Barbara J
Obeidat, Marya
Tipping the balance from angiogenesis to fibrosis in CKD
title Tipping the balance from angiogenesis to fibrosis in CKD
title_full Tipping the balance from angiogenesis to fibrosis in CKD
title_fullStr Tipping the balance from angiogenesis to fibrosis in CKD
title_full_unstemmed Tipping the balance from angiogenesis to fibrosis in CKD
title_short Tipping the balance from angiogenesis to fibrosis in CKD
title_sort tipping the balance from angiogenesis to fibrosis in ckd
topic Mini Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536966/
https://www.ncbi.nlm.nih.gov/pubmed/26312149
http://dx.doi.org/10.1038/kisup.2014.9
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