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Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiomet...

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Autores principales: Baranowski, Bradley J., Allen, Matti D., Nyarko, Jennifer N.K., Rector, R. Scott, Padilla, Jaume, Mousseau, Darrell D., Rau, Christoph D., Wang, Yibin, Laughlin, M. Harold, Emter, Craig A., MacPherson, Rebecca E.K., Olver, T. Dylan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262360/
https://www.ncbi.nlm.nih.gov/pubmed/34027891
http://dx.doi.org/10.1172/jci.insight.143141
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author Baranowski, Bradley J.
Allen, Matti D.
Nyarko, Jennifer N.K.
Rector, R. Scott
Padilla, Jaume
Mousseau, Darrell D.
Rau, Christoph D.
Wang, Yibin
Laughlin, M. Harold
Emter, Craig A.
MacPherson, Rebecca E.K.
Olver, T. Dylan
author_facet Baranowski, Bradley J.
Allen, Matti D.
Nyarko, Jennifer N.K.
Rector, R. Scott
Padilla, Jaume
Mousseau, Darrell D.
Rau, Christoph D.
Wang, Yibin
Laughlin, M. Harold
Emter, Craig A.
MacPherson, Rebecca E.K.
Olver, T. Dylan
author_sort Baranowski, Bradley J.
collection PubMed
description Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we tested the hypothesis that WD-AB would promote a multidementia phenotype involving cerebrovascular dysfunction alongside evidence of Alzheimer’s disease (AD) pathology. The results provide evidence of cerebrovascular insufficiency coupled with neuroinflammation and amyloidosis in swine with experimental cardiometabolic HF. Although cardiac ejection fraction was normal, indices of arterial compliance and cerebral blood flow were reduced, and cerebrovascular regulation was impaired in the WD-AB group. Cerebrovascular dysfunction occurred concomitantly with increased MAPK signaling and amyloidogenic processing (i.e., increased APP, BACE1, CTF, and Aβ40 in the prefrontal cortex and hippocampus) in the WD-AB group. Transcriptomic profiles of the stellate ganglia revealed the WD-AB group displayed an enrichment of gene networks associated with MAPK/ERK signaling, AD, frontotemporal dementia, and a number of behavioral phenotypes implicated in cognitive impairment. These provide potentially novel evidence from a swine model that cerebrovascular and neuronal pathologies likely both contribute to the dementia profile in a setting of cardiometabolic HF.
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spelling pubmed-82623602021-07-13 Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure Baranowski, Bradley J. Allen, Matti D. Nyarko, Jennifer N.K. Rector, R. Scott Padilla, Jaume Mousseau, Darrell D. Rau, Christoph D. Wang, Yibin Laughlin, M. Harold Emter, Craig A. MacPherson, Rebecca E.K. Olver, T. Dylan JCI Insight Research Article Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we tested the hypothesis that WD-AB would promote a multidementia phenotype involving cerebrovascular dysfunction alongside evidence of Alzheimer’s disease (AD) pathology. The results provide evidence of cerebrovascular insufficiency coupled with neuroinflammation and amyloidosis in swine with experimental cardiometabolic HF. Although cardiac ejection fraction was normal, indices of arterial compliance and cerebral blood flow were reduced, and cerebrovascular regulation was impaired in the WD-AB group. Cerebrovascular dysfunction occurred concomitantly with increased MAPK signaling and amyloidogenic processing (i.e., increased APP, BACE1, CTF, and Aβ40 in the prefrontal cortex and hippocampus) in the WD-AB group. Transcriptomic profiles of the stellate ganglia revealed the WD-AB group displayed an enrichment of gene networks associated with MAPK/ERK signaling, AD, frontotemporal dementia, and a number of behavioral phenotypes implicated in cognitive impairment. These provide potentially novel evidence from a swine model that cerebrovascular and neuronal pathologies likely both contribute to the dementia profile in a setting of cardiometabolic HF. American Society for Clinical Investigation 2021-05-24 /pmc/articles/PMC8262360/ /pubmed/34027891 http://dx.doi.org/10.1172/jci.insight.143141 Text en © 2021 Baranowski et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Baranowski, Bradley J.
Allen, Matti D.
Nyarko, Jennifer N.K.
Rector, R. Scott
Padilla, Jaume
Mousseau, Darrell D.
Rau, Christoph D.
Wang, Yibin
Laughlin, M. Harold
Emter, Craig A.
MacPherson, Rebecca E.K.
Olver, T. Dylan
Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title_full Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title_fullStr Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title_full_unstemmed Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title_short Cerebrovascular insufficiency and amyloidogenic signaling in Ossabaw swine with cardiometabolic heart failure
title_sort cerebrovascular insufficiency and amyloidogenic signaling in ossabaw swine with cardiometabolic heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262360/
https://www.ncbi.nlm.nih.gov/pubmed/34027891
http://dx.doi.org/10.1172/jci.insight.143141
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