A Preclinical Rat Model of Heart Failure With Preserved Ejection Fraction With Multiple Comorbidities.
RNA sequencing
diastolic dysfunction
group 2 pulmonary hypertension
heart failure with preserved ejection fraction
metabolic syndrome
soluble ST2
Journal
Frontiers in cardiovascular medicine
ISSN: 2297-055X
Titre abrégé: Front Cardiovasc Med
Pays: Switzerland
ID NLM: 101653388
Informations de publication
Date de publication:
2021
2021
Historique:
received:
05
11
2021
accepted:
20
12
2021
entrez:
31
1
2022
pubmed:
1
2
2022
medline:
1
2
2022
Statut:
epublish
Résumé
Heart failure with preserved ejection fraction (HFpEF) is a common complex clinical syndrome for which there are currently few evidence-based therapies. As patients with HFpEF very often present with comorbidities comprising the metabolic syndrome, we hypothesized, that metabolic syndrome could lead over time to the development of diastolic dysfunction and HFpEF. Obesity-prone rats were exposed to high-fat diet and compared to obesity-resistant rats fed with standard chow. Phenotyping of metabolic syndrome, associated with echocardiographic and cardiac hemodynamic measurements, was performed after 4 and 12 months. Blood and myocardial tissue sampling were performed for pathobiological evaluation. High-fat diet in obesity-prone rats elicited metabolic syndrome, characterized by increased body and abdominal fat weights, glucose intolerance and hyperlipidemia, as well as increased left ventricular (LV) systolic pressure (after 12 months). This was associated with LV diastolic dysfunction (assessed by increased LV end-diastolic pressure) and pulmonary hypertension (assessed by increased right ventricular systolic pressure). Echocardiography revealed significant concentric LV hypertrophy, while LV ejection fraction was preserved. LV remodeling was associated with cardiomyocyte hypertrophy, as well as myocardial and perivascular fibrosis. Circulating levels of soluble ST2 (the interleukin-1 receptor-like) markedly increased in rats with HFpEF, while plasma NT-proBNP levels decreased. RNA-sequencing analysis identified clusters of genes implicated in fatty acid metabolism and calcium-dependent contraction as upregulated pathways in the myocardium of rats with HFpEF. High-fat diet during 12 months in obesity-prone rats led to the development of a relevant preclinical model of HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.
Identifiants
pubmed: 35097026
doi: 10.3389/fcvm.2021.809885
pmc: PMC8793630
doi:
Types de publication
Journal Article
Langues
eng
Pagination
809885Informations de copyright
Copyright © 2022 Hubesch, Hanthazi, Acheampong, Chomette, Lasolle, Hupkens, Jespers, Vegh, Wembonyama, Verhoeven, Dewachter, Vachiery, Entee and Dewachter.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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