iScience (Feb 2022)
Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis
- Laura García-Mendívil,
- María Pérez-Zabalza,
- Konstantinos Mountris,
- Sam Duwé,
- Nick Smisdom,
- Marta Pérez,
- Lluís Luján,
- Esther Wolfs,
- Ronald B. Driesen,
- José María Vallejo-Gil,
- Pedro Carlos Fresneda-Roldán,
- Javier Fañanás-Mastral,
- Manuel Vázquez-Sancho,
- Marta Matamala-Adell,
- Juan Fernando Sorribas-Berjón,
- Javier André Bellido-Morales,
- Francisco Javier Mancebón-Sierra,
- Alexánder Sebastián Vaca-Núñez,
- Carlos Ballester-Cuenca,
- Aida Oliván-Viguera,
- Emiliano Diez,
- Laura Ordovás,
- Esther Pueyo
Affiliations
- Laura García-Mendívil
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain; Corresponding author
- María Pérez-Zabalza
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain
- Konstantinos Mountris
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain
- Sam Duwé
- Advanced Optical Microscopy Centre, Biomedical Research Institute, Hasselt University, Diepenbeek 3500, Belgium
- Nick Smisdom
- Biomedical Research Institute, Hasselt University, Diepenbeek 3500, Belgium
- Marta Pérez
- Department of Anatomy, Embryology and Animal Genetics, University of Zaragoza, Zaragoza 50013, Spain; Instituto Universitario de Investigación Mixto Agroalimentario de Aragón (IA2), University of Zaragoza, Zaragoza 50013, Spain
- Lluís Luján
- Instituto Universitario de Investigación Mixto Agroalimentario de Aragón (IA2), University of Zaragoza, Zaragoza 50013, Spain; Department of Animal Pathology, University of Zaragoza, Zaragoza 50013, Spain
- Esther Wolfs
- Biomedical Research Institute, Hasselt University, Diepenbeek 3500, Belgium
- Ronald B. Driesen
- Biomedical Research Institute, Hasselt University, Diepenbeek 3500, Belgium
- José María Vallejo-Gil
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Pedro Carlos Fresneda-Roldán
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Javier Fañanás-Mastral
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Manuel Vázquez-Sancho
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Marta Matamala-Adell
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Juan Fernando Sorribas-Berjón
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Javier André Bellido-Morales
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Francisco Javier Mancebón-Sierra
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Alexánder Sebastián Vaca-Núñez
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Carlos Ballester-Cuenca
- Department of Cardiovascular Surgery, University Hospital Miguel Servet, Zaragoza 50009, Spain
- Aida Oliván-Viguera
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza 50018, Spain
- Emiliano Diez
- Institute of Experimental Medicine and Biology of Cuyo (IMBECU), CONICET, Mendoza 5500, Argentina
- Laura Ordovás
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain; ARAID Foundation, Zaragoza 50018, Spain; Corresponding author
- Esther Pueyo
- Biomedical Signal Interpretation and Computational Simulation Group (BSICoS), Aragón Institute of Engineering Research, University of Zaragoza, Zaragoza 50018, Spain; BSICoS, IIS Aragón, Zaragoza 50018, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza 50018, Spain
- Journal volume & issue
-
Vol. 25,
no. 2
p. 103822
Abstract
Summary: Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics.
