Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

García-Mendívil, Laura (Universidad de Zaragoza) ; Pérez-Zabalza, María ; Mountris, Konstantinos ; Duwé, Sam ; Smisdom, Nick ; Pérez, Marta (Universidad de Zaragoza) ; Luján, Lluis (Universidad de Zaragoza) ; Wolfs, Esther ; Driesen, Ronald B. ; Vallejo-Gil, José María ; Fresneda-Roldán, Pedro Carlos ; Fañanás-Mastral, Javier ; Vázquez-Sancho, Manuel ; Matamala-Adell, Marta (Universidad de Zaragoza) ; Sorribas-Berjón, Juan Fernando ; Bellido-Morales, Javier André ; Mancebón-Sierra, Francisco Javier ; Vaca-Núñez, Alexander Sebastián ; Ballester-Cuenca, Carlos (Universidad de Zaragoza) ; Oliván-Viguera, Aida ; Diez, Emiliano ; Ordovás, Laura ; Pueyo, Esther (Universidad de Zaragoza)

Resumen: 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. © 2022 The Author(s)

Idioma: Inglés

DOI: 10.1016/j.isci.2022.103822

Año: 2022

Publicado en: ISCIENCE 25, 2 (2022), 103822 [20 pp]
ISSN: 2589-0042

Factor impacto JCR: 5.8 (2022)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 15 / 73 = 0.205 (2022) - Q1 - T1

Factor impacto CITESCORE: 6.9 - General (Q1)

Factor impacto SCIMAGO: 1.624 - Multidisciplinary (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/T39-20R-BSICoS group
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP128_21
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP94_21
Financiación: info:eu-repo/grantAgreement/EUR/ERC-2014-StG-638284
Financiación: info:eu-repo/grantAgreement/ES/MICINN-FEDER/PID2019-105674RB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Área Cirugía (Dpto. Cirugía)
Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)