title: Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure.
abstract: Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium.
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Annalinda
authors.initials: A
authors.lastname: Pisano
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Cerbelli
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Perli
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pelullo
authors.affiliation: Department of Biochemical Sciences, University of Florence, Viale Morgagni, 50, 50134, Florence, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bargelli
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Preziuso
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy; Department of Molecular Medicine, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mancini
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Langping
authors.initials: L
authors.lastname: He
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Matthew G D
authors.initials: MG
authors.lastname: Bates
authors.affiliation: Forensic Pathology Service, Institute of Legal Medicine, Seville, Spain.
authors.forename: Joaquin R
authors.initials: JR
authors.lastname: Lucena
authors.affiliation: Department of Cardiac Surgery and Transplantation, San Camillo Hospital, Rome, Italy.
authors.forename: Paola Lilla
authors.initials: PL
authors.lastname: Della Monica
authors.affiliation: Department of Human Anatomic, Histologic, Forensic and Locomotor Apparatus Sciences, Sapienza University, 00161, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Familiari
authors.affiliation: Department of Biotechnologies and medical and Surgical Sciences, Sapienza University, 00161, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Petrozza
authors.affiliation: Department of Biochemical Sciences, University of Florence, Viale Morgagni, 50, 50134, Florence, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Nediani
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: d'Amati
authors.affiliation: Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy. Electronic address: carla.giordano@uniroma1.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000473:pathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology*; D061346:Laser Capture Microdissection; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications*; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial
keywords: Cardiac remodeling; Mitochondrial biogenesis; Mitochondrial cardiomyopathy; Myocardial hypertrophy; Oxidative stress; mtDNA depletion