Cargando…

Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy

Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that d...

Descripción completa

Detalles Bibliográficos
Autores principales: Gutsol, Alex A., Blanco, Paula, Hale, Taben M., Thibodeau, Jean-Francois, Holterman, Chet E., Nasrallah, Rania, Correa, Jose W. N., Afanasiev, Sergey A., Touyz, Rhian M., Kennedy, Chris R. J., Burger, Dylan, Hébert, Richard L., Burns, Kevin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853553/
https://www.ncbi.nlm.nih.gov/pubmed/35176122
http://dx.doi.org/10.1371/journal.pone.0264136
_version_ 1784653255637204992
author Gutsol, Alex A.
Blanco, Paula
Hale, Taben M.
Thibodeau, Jean-Francois
Holterman, Chet E.
Nasrallah, Rania
Correa, Jose W. N.
Afanasiev, Sergey A.
Touyz, Rhian M.
Kennedy, Chris R. J.
Burger, Dylan
Hébert, Richard L.
Burns, Kevin D.
author_facet Gutsol, Alex A.
Blanco, Paula
Hale, Taben M.
Thibodeau, Jean-Francois
Holterman, Chet E.
Nasrallah, Rania
Correa, Jose W. N.
Afanasiev, Sergey A.
Touyz, Rhian M.
Kennedy, Chris R. J.
Burger, Dylan
Hébert, Richard L.
Burns, Kevin D.
author_sort Gutsol, Alex A.
collection PubMed
description Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that do not necessarily comply with lesional descriptors for glomerular injury that are well-established in clinical pathology. Here, we provide a critical appraisal of experimental hypertensive glomerulopathy with the same approach used to assess hypertensive glomerulopathy in humans. Four hypertensive models with varying pathogenesis were analyzed–chronic angiotensin II infused mice, mice expressing active human renin in the liver (TTRhRen), spontaneously hypertensive rats (SHR), and Goldblatt two-kidney one-clip rats (2K1C). Analysis of glomerulopathy utilized the same criteria applied in humans–hyalinosis, focal segmental glomerulosclerosis (FSGS), ischemic, hypertrophic and solidified glomeruli, or global glomerulosclerosis (GGS). Data from animal models were compared to human reference values. Kidneys in TTRhRen mice, SHR and the nonclipped kidneys in 2K1C rats had no sign of hyalinosis, FSGS or GGS. Glomerulopathy in these groups was limited to variations in mesangial and capillary compartment volumes, with mild increases in collagen deposition. Histopathology in angiotensin II infused mice corresponded to mesangioproliferative glomerulonephritis, but not hypertensive glomerulosclerosis. The number of nephrons was significantly reduced in TTRhRen mice and SHR, but did not correlate with severity of glomerulopathy. The most substantial human-like glomerulosclerotic lesions, including FSGS, ischemic obsolescent glomeruli and GGS, were found in the clipped kidneys of 2K1C rats. The comparison of affected kidneys to healthy control in animals produces lesion values that are numerically impressive but correspond to mild damage if compared to humans. Animal studies should be standardized by employing the criteria and classifications established in human pathology to make experimental and human data fully comparable for comprehensive analysis and model improvements.
format Online
Article
Text
id pubmed-8853553
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-88535532022-02-18 Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy Gutsol, Alex A. Blanco, Paula Hale, Taben M. Thibodeau, Jean-Francois Holterman, Chet E. Nasrallah, Rania Correa, Jose W. N. Afanasiev, Sergey A. Touyz, Rhian M. Kennedy, Chris R. J. Burger, Dylan Hébert, Richard L. Burns, Kevin D. PLoS One Research Article Current research on hypertension utilizes more than fifty animal models that rely mainly on stable increases in systolic blood pressure. In experimental hypertension, grading or scoring of glomerulopathy in the majority of studies is based on a wide range of opinion-based histological changes that do not necessarily comply with lesional descriptors for glomerular injury that are well-established in clinical pathology. Here, we provide a critical appraisal of experimental hypertensive glomerulopathy with the same approach used to assess hypertensive glomerulopathy in humans. Four hypertensive models with varying pathogenesis were analyzed–chronic angiotensin II infused mice, mice expressing active human renin in the liver (TTRhRen), spontaneously hypertensive rats (SHR), and Goldblatt two-kidney one-clip rats (2K1C). Analysis of glomerulopathy utilized the same criteria applied in humans–hyalinosis, focal segmental glomerulosclerosis (FSGS), ischemic, hypertrophic and solidified glomeruli, or global glomerulosclerosis (GGS). Data from animal models were compared to human reference values. Kidneys in TTRhRen mice, SHR and the nonclipped kidneys in 2K1C rats had no sign of hyalinosis, FSGS or GGS. Glomerulopathy in these groups was limited to variations in mesangial and capillary compartment volumes, with mild increases in collagen deposition. Histopathology in angiotensin II infused mice corresponded to mesangioproliferative glomerulonephritis, but not hypertensive glomerulosclerosis. The number of nephrons was significantly reduced in TTRhRen mice and SHR, but did not correlate with severity of glomerulopathy. The most substantial human-like glomerulosclerotic lesions, including FSGS, ischemic obsolescent glomeruli and GGS, were found in the clipped kidneys of 2K1C rats. The comparison of affected kidneys to healthy control in animals produces lesion values that are numerically impressive but correspond to mild damage if compared to humans. Animal studies should be standardized by employing the criteria and classifications established in human pathology to make experimental and human data fully comparable for comprehensive analysis and model improvements. Public Library of Science 2022-02-17 /pmc/articles/PMC8853553/ /pubmed/35176122 http://dx.doi.org/10.1371/journal.pone.0264136 Text en © 2022 Gutsol et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gutsol, Alex A.
Blanco, Paula
Hale, Taben M.
Thibodeau, Jean-Francois
Holterman, Chet E.
Nasrallah, Rania
Correa, Jose W. N.
Afanasiev, Sergey A.
Touyz, Rhian M.
Kennedy, Chris R. J.
Burger, Dylan
Hébert, Richard L.
Burns, Kevin D.
Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title_full Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title_fullStr Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title_full_unstemmed Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title_short Comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. Glomerulopathy
title_sort comparative analysis of hypertensive nephrosclerosis in animal models of hypertension and its relevance to human pathology. glomerulopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8853553/
https://www.ncbi.nlm.nih.gov/pubmed/35176122
http://dx.doi.org/10.1371/journal.pone.0264136
work_keys_str_mv AT gutsolalexa comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT blancopaula comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT haletabenm comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT thibodeaujeanfrancois comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT holtermanchete comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT nasrallahrania comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT correajosewn comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT afanasievsergeya comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT touyzrhianm comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT kennedychrisrj comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT burgerdylan comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT hebertrichardl comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy
AT burnskevind comparativeanalysisofhypertensivenephrosclerosisinanimalmodelsofhypertensionanditsrelevancetohumanpathologyglomerulopathy