Defective DNA Replication Impairs Mitochondrial Biogenesis In Human Failing Hearts

RATIONALE:Mitochondrial dysfunction plays a pivotal role in the development of heart failure. Animal studies suggest that impaired mitochondrial biogenesis attributable to downregulation of the peroxisome proliferator-activated receptor γ coactivator (PGC)-1 transcriptional pathway is integral of mi...

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Bibliographic Details
Published in:Circulation research 2010-05, Vol.106 (9), p.1541-1548
Main Authors: Karamanlidis, Georgios, Nascimben, Luigino, Couper, Gregory S, Shekar, Prem S, del Monte, Federica, Tian, Rong
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Cardiology. Vascular system
DNA Replication
DNA, Mitochondrial - biosynthesis
DNA, Mitochondrial - genetics
Down-Regulation
Female
Fundamental and applied biological sciences. Psychology
Heart
Heart Failure - genetics
Heart Failure - pathology
Heart failure, cardiogenic pulmonary edema, cardiac enlargement
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Humans
Male
Medical sciences
Middle Aged
Mitochondria - genetics
Mitochondria - pathology
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Transcription Factors - genetics
Transcription Factors - metabolism
Vertebrates: cardiovascular system
Young Adult
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Summary:RATIONALE:Mitochondrial dysfunction plays a pivotal role in the development of heart failure. Animal studies suggest that impaired mitochondrial biogenesis attributable to downregulation of the peroxisome proliferator-activated receptor γ coactivator (PGC)-1 transcriptional pathway is integral of mitochondrial dysfunction in heart failure. OBJECTIVE:The study sought to define mechanisms underlying the impaired mitochondrial biogenesis and function in human heart failure. METHODS AND RESULTS:We collected left ventricular tissue from end-stage heart failure patients and from nonfailing hearts (n=23, and 19, respectively). The mitochondrial DNA (mtDNA) content was decreased by >40% in the failing hearts, after normalization for a moderate decrease in citrate synthase activity (P
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.109.212753