000130146 001__ 130146
000130146 005__ 20240720100852.0
000130146 0247_ $$2doi$$a10.34133/research.0254
000130146 0248_ $$2sideral$$a136465
000130146 037__ $$aART-2023-136465
000130146 041__ $$aeng
000130146 100__ $$0(orcid)0000-0002-2954-1068$$aGarcía-Mendívil, Laura$$uUniversidad de Zaragoza
000130146 245__ $$aInterindividual Age-Independent Differences in Human CX43 Impact Ventricular Arrhythmic Risk
000130146 260__ $$c2023
000130146 5060_ $$aAccess copy available to the general public$$fUnrestricted
000130146 5203_ $$aConnexin 43 (CX43) is one of the major components of gap junctions, the structures responsible for the intercellular communication and transmission of the electrical impulse in the left ventricle. There is limited information on the histological changes of CX43 with age and their effect on electrophysiology, especially in humans. Here, we analyzed left ventricular biopsies from living donors starting at midlife to characterize age-related CX43 remodeling. We assessed its quantity, degree of lateralization, and spatial heterogeneity together with fibrotic deposition. We observed no significant age-related remodeling of CX43. Only spatial heterogeneity increased slightly with age, and this increase was better explained by biological age than by chronological age. Importantly, we found that CX43 features varied considerably among individuals in our population with no relevant relationship to age or fibrosis content, in contrast to animal species. We used our experimental results to feed computational models of human ventricular electrophysiology and to assess the effects of interindividual differences in specific features of CX43 and fibrosis on conduction velocity, action potential duration, and arrhythmogenicity. We found that larger amounts of fibrosis were associated with the highest arrhythmic risk, with this risk being increased when fibrosis deposition was combined with a reduction in CX43 amount and/or with an increase in CX43 spatial heterogeneity. These mechanisms underlying high arrhythmic risk in some individuals were not associated with age in our study population. In conclusion, our data rule out CX43 remodeling as an age-related arrhythmic substrate in the population beyond midlife, but highlight its potential as a proarrhythmic factor at the individual level, especially when combined with increased fibrosis.
000130146 536__ $$9info:eu-repo/grantAgreement/ES/DGA/LMP128_21$$9info:eu-repo/grantAgreement/ES/DGA/LMP94_21$$9info:eu-repo/grantAgreement/ES/DGA/T39-23R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105674RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-140556OB-I00$$9info:eu-repo/grantAgreement/EUR/MICINN/TED2021-130459B-I00
000130146 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000130146 590__ $$a8.5$$b2023
000130146 592__ $$a2.102$$b2023
000130146 591__ $$aMULTIDISCIPLINARY SCIENCES$$b14 / 134 = 0.104$$c2023$$dQ1$$eT1
000130146 593__ $$aMultidisciplinary$$c2023$$dQ1
000130146 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000130146 700__ $$aPérez-Zabalza, María
000130146 700__ $$aOliver-Gelabert, Antoni
000130146 700__ $$aVallejo-Gil, José María
000130146 700__ $$aFañanás-Mastral, Javier
000130146 700__ $$aVázquez-Sancho, Manuel
000130146 700__ $$aBellido-Morales, Javier André
000130146 700__ $$aVaca-Núñez, Alexánder Sebastián
000130146 700__ $$0(orcid)0000-0002-2225-308X$$aBallester-Cuenca, Carlos$$uUniversidad de Zaragoza
000130146 700__ $$aDiez, Emiliano
000130146 700__ $$0(orcid)0000-0003-3982-1263$$aOrdovás, Laura
000130146 700__ $$0(orcid)0000-0002-1960-407X$$aPueyo, Esther$$uUniversidad de Zaragoza
000130146 7102_ $$11013$$2090$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Cirugía
000130146 7102_ $$15008$$2800$$aUniversidad de Zaragoza$$bDpto. Ingeniería Electrón.Com.$$cÁrea Teoría Señal y Comunicac.
000130146 773__ $$g6 (2023), 0254 [17 pp.]$$tResearch$$x2096-5168
000130146 8564_ $$s4275925$$uhttps://zaguan.unizar.es/record/130146/files/texto_completo.pdf$$yVersión publicada
000130146 8564_ $$s3005512$$uhttps://zaguan.unizar.es/record/130146/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000130146 909CO $$ooai:zaguan.unizar.es:130146$$particulos$$pdriver
000130146 951__ $$a2024-07-19-18:49:40
000130146 980__ $$aARTICLE