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dc.contributor.author | Garcia-Lunar, Ines | |
dc.contributor.author | Jorge, Inmaculada | |
dc.contributor.author | Sáiz, Jorge | |
dc.contributor.author | Solanes, Núria | |
dc.contributor.author | Dantas, Ana Paula | |
dc.contributor.author | Rodríguez-Arias, Juan José | |
dc.contributor.author | Ascaso-Sánchez, María Soledad | |
dc.contributor.author | Galan-Arriola, Carlos | |
dc.contributor.author | Jiménez, Francisco Rafael | |
dc.contributor.author | Sandoval, Elena | |
dc.contributor.author | Nuche, Jorge | |
dc.contributor.author | Moran-Garrido, Maria | |
dc.contributor.author | Camafeita, Emilio | |
dc.contributor.author | Rigol, Montserrat | |
dc.contributor.author | Sánchez-Gonzalez, Javier | |
dc.contributor.author | Fuster, Valentin | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Barbas, Coral | |
dc.contributor.author | Ibáñez, Borja | |
dc.contributor.author | Pereda, Daniel | |
dc.contributor.author | Garcia-Alvarez, Ana | |
dc.date.accessioned | 2024-05-17T09:26:46Z | |
dc.date.available | 2024-05-17T09:26:46Z | |
dc.date.issued | 2024-03-27 | |
dc.identifier.citation | Basic Res Cardiol. 2024 Mar 27 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19440 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | Funding Open Access funding provided thanks to the CRUECSIC agreement with Springer Nature. This study received funding from Instituto de Salud Carlos III through projects PI17/00995 and PI20/00742 (Co-funded by the European Regional Development Fund; “A way to make Europe”), the Spanish Ministry of Science, Innovation and Universities (PID2021-122348NB-I00, PLEC2022-009235 and PLEC2022-009298), the Comunidad de Madrid (IMMUNO-VAR, P2022/BMD-7333), and “la Caixa” Banking Foundation (project codes HR17-00247 and HR22-00253). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation), and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/ AEI/https://doi.org/10.13039/501100011033). Part of the work presented here was performed at the Centre de Recerca Biommedica Cellex (IDIBAPS) in Barcelona. IDIBAPS belongs to the CERCA Program and receives funding from the Generalitat de Catalunya. Maria Moran-Garrido is a recipient of predoctoral fellowship from the Ministerio de Ciencia, Innovacion y Universidades (grant number FPU19/06206). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38536505 | es_ES |
dc.identifier.doi | 10.1007/s00395-024-01041-5 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación ProCNIC | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1435-1803 | es_ES |
dc.relation.publisherversion | 10.1007/s00395-024-01041-5 | es_ES |
dc.identifier.journal | Basic research in cardiology | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI17/00995 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI20/00742 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2021-122348NB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PLEC2022-009235 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PLEC2022-009298 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IMMUNO-VAR/P2022/BMD-7333 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00247 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR22-00253 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/10.13039/501100011033/CEX2020-001041-S/CEX2020-001041-S | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/FPU19/06206 | es_ES |