Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Autor: García-Lunar I; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; Cardiology Department, University Hospital La Moraleja, Madrid, Spain., Jorge I; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Sáiz J; Centre of Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain., Solanes N; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain., Dantas AP; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain., Rodríguez-Arias JJ; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain., Ascaso M; Department of Cardiovascular Surgery, Hospital Clínic Barcelona, Barcelona, Spain., Galán-Arriola C; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Jiménez FR; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain., Sandoval E; Department of Cardiovascular Surgery, Hospital Clínic Barcelona, Barcelona, Spain., Nuche J; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; Department of Cardiology, Hospital 12 de Octubre, Madrid, Spain., Moran-Garrido M; Centre of Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain., Camafeita E; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Rigol M; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain., Sánchez-Gonzalez J; Philips Healthcare Iberia, Madrid, Spain., Fuster V; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; Mount Sinai Fuster Heart Hospital, Mount Sinai Hospital, New York, NY, USA., Vázquez J; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain., Barbas C; Centre of Metabolomics and Bioanalysis (CEMBIO), Department of Chemistry and Biochemistry, Facultad de Farmacia, Universidad San Pablo-CEU, Madrid, Spain., Ibáñez B; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; IIS-Fundación Jiménez Diaz University Hospital, Madrid, Spain., Pereda D; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.; Department of Cardiovascular Surgery, Hospital Clínic Barcelona, Barcelona, Spain.; Universitat de Barcelona, Barcelona, Spain., García-Álvarez A; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. anagarci@clinic.cat.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. anagarci@clinic.cat.; Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Universitat de Barcelona, Villarroel 170, 08036, Barcelona, Spain. anagarci@clinic.cat.; Universitat de Barcelona, Barcelona, Spain. anagarci@clinic.cat.
Jazyk: angličtina
Zdroj: Basic research in cardiology [Basic Res Cardiol] 2024 Jun; Vol. 119 (3), pp. 419-433. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1007/s00395-024-01041-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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