000117696 001__ 117696
000117696 005__ 20240319081008.0
000117696 0247_ $$2doi$$a10.1161/CIRCULATIONAHA.121.056286
000117696 0248_ $$2sideral$$a129188
000117696 037__ $$aART-2022-129188
000117696 041__ $$aeng
000117696 100__ $$aLechuga-Vieco, A.
000117696 245__ $$aHeteroplasmy of Wild-Type Mitochondrial DNA Variants in Mice Causes Metabolic Heart Disease with Pulmonary Hypertension and Frailty; 35236094
000117696 260__ $$c2022
000117696 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117696 5203_ $$aBackground: In most eukaryotic cells, the mitochondrial DNA (mtDNA) is transmitted uniparentally and present in multiple copies derived from the clonal expansion of maternally inherited mtDNA. All copies are therefore near-identical, or homoplasmic. The presence of >1 mtDNA variant in the same cytoplasm can arise naturally or result from new medical technologies aimed at preventing mitochondrial genetic diseases and improving fertility. The latter is called divergent nonpathologic mtDNA heteroplasmy (DNPH). We hypothesized that DNPH is maladaptive and usually prevented by the cell. Methods: We engineered and characterized DNPH mice throughout their lifespan using transcriptomic, metabolomic, biochemical, physiologic, and phenotyping techniques. We focused on in vivo imaging techniques for noninvasive assessment of cardiac and pulmonary energy metabolism. Results: We show that DNPH impairs mitochondrial function, with profound consequences in critical tissues that cannot resolve heteroplasmy, particularly cardiac and skeletal muscle. Progressive metabolic stress in these tissues leads to severe pathology in adulthood, including pulmonary hypertension and heart failure, skeletal muscle wasting, frailty, and premature death. Symptom severity is strongly modulated by the nuclear context. Conclusions: Medical interventions that may generate DNPH should address potential incompatibilities between donor and recipient mtDNA. © 2022 Lippincott Williams and Wilkins. All rights reserved.
000117696 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000117696 590__ $$a37.8$$b2022
000117696 592__ $$a7.8$$b2022
000117696 591__ $$aPERIPHERAL VASCULAR DISEASE$$b1 / 68 = 0.015$$c2022$$dQ1$$eT1
000117696 593__ $$aPhysiology (medical)$$c2022$$dQ1
000117696 591__ $$aCARDIAC & CARDIOVASCULAR SYSTEMS$$b3 / 143 = 0.021$$c2022$$dQ1$$eT1
000117696 593__ $$aCardiology and Cardiovascular Medicine$$c2022$$dQ1
000117696 594__ $$a42.1$$b2022
000117696 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117696 700__ $$0(orcid)0000-0002-4703-6620$$aLatorre-Pellicer, A.$$uUniversidad de Zaragoza
000117696 700__ $$aCalvo, E.
000117696 700__ $$aTorroja, C.
000117696 700__ $$aPellico, J.
000117696 700__ $$aAcín-Pérez, R.
000117696 700__ $$aGarcía-Gil, M. L.
000117696 700__ $$aSantos, A.
000117696 700__ $$aBagwan, N.
000117696 700__ $$aBonzon-Kulichenko, E.
000117696 700__ $$aMagni, R.
000117696 700__ $$aBenito, M.
000117696 700__ $$aJusto-Méndez, R.
000117696 700__ $$aSimon, A. K.
000117696 700__ $$aSánchez-Cabo, F.
000117696 700__ $$aVázquez, J.
000117696 700__ $$aRuíz-Cabello, J.
000117696 700__ $$aEnríquez, J. A.
000117696 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000117696 773__ $$g145, 14 (2022), 1084-1101$$pCirculation$$tCirculation$$x0009-7322
000117696 8564_ $$s5477095$$uhttps://zaguan.unizar.es/record/117696/files/texto_completo.pdf$$yVersión publicada
000117696 8564_ $$s2433445$$uhttps://zaguan.unizar.es/record/117696/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117696 909CO $$ooai:zaguan.unizar.es:117696$$particulos$$pdriver
000117696 951__ $$a2024-03-18-14:48:17
000117696 980__ $$aARTICLE