Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.
Cardiac imaging
Omics
Pulmonary hypertension
Right ventricle
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
27 Mar 2024
27 Mar 2024
Historique:
received:
09
11
2023
accepted:
10
02
2024
revised:
10
02
2024
medline:
27
3
2024
pubmed:
27
3
2024
entrez:
27
3
2024
Statut:
aheadofprint
Résumé
Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.
Identifiants
pubmed: 38536505
doi: 10.1007/s00395-024-01041-5
pii: 10.1007/s00395-024-01041-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Instituto de Salud Carlos III
ID : PI17/00995
Organisme : Instituto de Salud Carlos III
ID : PI20/00742
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : PID2021-122348NB-I00
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : PLEC2022-009235
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : PLEC2022-009298
Organisme : Comunidad de Madrid
ID : IMMUNO-VAR
Organisme : Comunidad de Madrid
ID : P2022/BMD-7333
Organisme : 'la Caixa' Foundation
ID : HR17-00247
Organisme : 'la Caixa' Foundation
ID : HR22-00253
Informations de copyright
© 2024. The Author(s).
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