Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis

Abstract Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular r...

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Autores principales:	Hans-Ulrich Prommer, Johannes Maurer, Karoline von Websky, Christian Freise, Kerstin Sommer, Hamoud Nasser, Rudi Samapati, Bettina Reglin, Pedro Guimarães, Axel Radlach Pries, Uwe Querfeld
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9bbe5b886a504829860322fbd4850bc0
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spelling	oai:doaj.org-article:9bbe5b886a504829860322fbd4850bc02021-12-02T15:08:06ZChronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis10.1038/s41598-018-23663-12045-2322https://doaj.org/article/9bbe5b886a504829860322fbd4850bc02018-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23663-1https://doaj.org/toc/2045-2322Abstract Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy. Structural changes were characterized by a heterogeneous pattern of focal microvascular rarefaction with loss of coherent microvascular networks resulting in large avascular areas. Corresponding microvascular dysfunction was evident by significantly diminished blood flow velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the cremaster muscle paralleled rarefaction in the myocardium, which was accompanied by a decrease in transcription levels not only of the transcriptional regulator HIF-1α, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia in mice associates with systemic microvascular disease with rarefaction, tissue hypoxia and dysfunctional angiogenesis.Hans-Ulrich PrommerJohannes MaurerKaroline von WebskyChristian FreiseKerstin SommerHamoud NasserRudi SamapatiBettina ReglinPedro GuimarãesAxel Radlach PriesUwe QuerfeldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hans-Ulrich Prommer Johannes Maurer Karoline von Websky Christian Freise Kerstin Sommer Hamoud Nasser Rudi Samapati Bettina Reglin Pedro Guimarães Axel Radlach Pries Uwe Querfeld Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
description	Abstract Chronic kidney disease (CKD) is associated with excessive mortality from cardiovascular disease (CVD). Endothelial dysfunction, an early manifestation of CVD, is consistently observed in CKD patients and might be linked to structural defects of the microcirculation including microvascular rarefaction. However, patterns of microvascular rarefaction in CKD and their relation to functional deficits in perfusion and oxygen delivery are currently unknown. In this in-vivo microscopy study of the cremaster muscle microcirculation in BALB/c mice with moderate to severe uremia, we show in two experimental models (adenine feeding or subtotal nephrectomy), that serum urea levels associate incrementally with a distinct microangiopathy. Structural changes were characterized by a heterogeneous pattern of focal microvascular rarefaction with loss of coherent microvascular networks resulting in large avascular areas. Corresponding microvascular dysfunction was evident by significantly diminished blood flow velocity, vascular tone, and oxygen uptake. Microvascular rarefaction in the cremaster muscle paralleled rarefaction in the myocardium, which was accompanied by a decrease in transcription levels not only of the transcriptional regulator HIF-1α, but also of its target genes Angpt-2, TIE-1 and TIE-2, Flkt-1 and MMP-9, indicating an impaired hypoxia-driven angiogenesis. Thus, experimental uremia in mice associates with systemic microvascular disease with rarefaction, tissue hypoxia and dysfunctional angiogenesis.
format	article
author	Hans-Ulrich Prommer Johannes Maurer Karoline von Websky Christian Freise Kerstin Sommer Hamoud Nasser Rudi Samapati Bettina Reglin Pedro Guimarães Axel Radlach Pries Uwe Querfeld
author_facet	Hans-Ulrich Prommer Johannes Maurer Karoline von Websky Christian Freise Kerstin Sommer Hamoud Nasser Rudi Samapati Bettina Reglin Pedro Guimarães Axel Radlach Pries Uwe Querfeld
author_sort	Hans-Ulrich Prommer
title	Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
title_short	Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
title_full	Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
title_fullStr	Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
title_full_unstemmed	Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
title_sort	chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/9bbe5b886a504829860322fbd4850bc0
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Chronic kidney disease induces a systemic microangiopathy, tissue hypoxia and dysfunctional angiogenesis

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