Document Detail


Impaired mitochondrial biogenesis precedes heart failure in right ventricular hypertrophy in congenital heart disease.
MedLine Citation:
PMID:  21840936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The outcome of the surgical repair in congenital heart disease correlates with the degree of myocardial damage. In this study, we determined whether mitochondrial DNA depletion is a sensitive marker of right ventricular (RV) damage and whether impaired mitochondrial DNA (mtDNA) replication contributes to the transition from compensated hypertrophy to failure.
METHODS AND RESULTS: RV samples obtained from 31 patients undergoing cardiac surgery were compared with 5 RV samples from nonfailing hearts (control). Patients were divided into compensated hypertrophy and failure groups, based on preoperative echocardiography, catheterization, and/or MRI data. Mitochondrial enzyme activities (citrate synthase and succinate dehydrogenase) were maintained during hypertrophy and decreased by ≈40% (P<0.05 versus control) at the stage of failure. In contrast, mtDNA content was progressively decreased in the hypertrophied RV through failure (by 28±8% and 67±11%, respectively, P<0.05 for both), whereas mtDNA-encoded gene expression was sustained by increased transcriptional activity during compensated hypertrophy but not in failure. Mitochondrial DNA depletion was attributed to reduced mtDNA replication in both hypertrophied and failing RV, and it was independent of PGC-1 downregulation but was accompanied by reduced expression of proteins constituting the mtDNA replication fork. Decreased mtDNA content in compensated hypertrophy was also associated with pathological changes of mitochondria ultrastructure.
CONCLUSIONS: Impaired mtDNA replication causes early and progressive depletion of mtDNA in the RV of the patients with congenital heart disease during the transition from hypertrophy to failure. Decreased mtDNA content probably is a sensitive marker of mitochondrial injury in this patient population.
Authors:
Georgios Karamanlidis; Victor Bautista-Hernandez; Francis Fynn-Thompson; Pedro Del Nido; Rong Tian
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-12
Journal Detail:
Title:  Circulation. Heart failure     Volume:  4     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-01-11     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  707-13     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Biological Markers
Case-Control Studies
Child
Child, Preschool
Citrate (si)-Synthase / metabolism
DNA Replication / genetics
DNA, Mitochondrial / genetics
Disease Progression*
Female
Heart Diseases / complications*,  congenital*,  pathology
Heart Failure / diagnosis,  etiology*,  pathology
Humans
Hypertrophy, Right Ventricular / diagnosis,  etiology*,  pathology
Infant
Male
Mitochondria, Heart / enzymology,  pathology*,  ultrastructure
Prognosis
Succinate Dehydrogenase / metabolism
Young Adult
Grant Support
ID/Acronym/Agency:
R01 HL059246/HL/NHLBI NIH HHS; R01 HL059246-11/HL/NHLBI NIH HHS; R01 HL067970/HL/NHLBI NIH HHS; R01 HL067970-09/HL/NHLBI NIH HHS; R01 HL110349/HL/NHLBI NIH HHS; R01 HL110349-01/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/DNA, Mitochondrial; EC 1.3.99.1/Succinate Dehydrogenase; EC 2.3.3.1/Citrate (si)-Synthase
Comments/Corrections
Comment In:
Circ Heart Fail. 2012 Jan;5(1):e15; author reply e16   [PMID:  22253409 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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