Cited by 306Mitochondrial Function and PathologyCancer, Hypoxia, and MetabolismHigh Altitude and Hypoxia

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Hypoxemia Is Associated With Mitochondrial DNA Damage and Gene Induction: Implications for Cardiac Disease

Corral-Debrinski, Marisol·1991·JAMA

DOI 10.1001/jama.1991.03470130092035

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Abstract

Objective --Oxidative phosphorylation (OXPHOS) deficiency due to hypoxemia or other causes was hypothesized to increase oxygen radical generation, damage mitochondrial DNA (mtDNA), and reduce adenosine triphosphate synthesis, resulting in compensatory OXPHOS gene induction. Therefore, we investigated the levels of mtDNA damage and OXPHOS transcripts in normal and ischemic hearts, and then in other forms of heart disease.Design --DNA was extracted from the heart and the levels of the common 4977 base pair mtDNA deletion were quantitated as an index for mtDNA damage. Total RNA was extracted from hearts and analyzed for OXPHOS transcript levels.Results --In control hearts, the 4977 base pair mtDNA deletion appeared at age 40 years and reached a maximum deletion of 0.0035%. Much higher levels were found in ischemic hearts (0.02% to 0.85%), as well as in three of 10 cases with other types of heart disease (0.017% to 0.16%). The OXPHOS transcripts were increased in all diseased hearts.Conclusion --Ischemic hearts have increased mtDNA damage and OXPHOS gene expression, suggesting that mtDNA damage is associated with OXPHOS deficiency. Oxidative phosphorylation defects may also play a role in some other forms of cardiac disease.

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Age-dependent human atrial mitochondrial DNA deletion relating to the prevalence of atrial fibrillation: A possible role for energy metabolic remodeling in the human atrium
Hisatome, I., & Igawa, O. (2008) · doi:10.5105/jse.28.129
Cardiac Disease in Older Adults
Aronow, W. S., & Frishman, W. H. (2018) · Springer eBooks · doi:10.1007/978-3-319-20317-1_15-1
The Genetics of Cardiac Electrophysiology in Humans
Pyeritz, R. E. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00057-4
Mitochondria in the Aging Heart
Marı́n-Garcı́a, J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4599-9_13
Heart Mitochondria: Receivers and Transmitters of Signals
Marı́n-Garcı́a, J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4599-9_8
Physiologic Changes in Cardiac Function with Aging
Aronow, W. S., & Frishman, W. H. (2011) · Springer eBooks · doi:10.1007/978-1-4419-6999-6_50
Cardiac Changes in the Elderly
Aronow, W. S., & Frishman, W. H. (2011) · Springer eBooks · doi:10.1007/978-1-4419-0892-6_21 · Cited by 1
“Reduced oxidative phosphorylation and cumulative mitochondrial peroxidation occurring with age may also reduce the left ventricular diastolic function [68, 69 ].”
Background
Impact of captopril on cardiac mitochondrial function in an in-vivo animal model of atherosclerosis
Kojić, Z., & Šćepanović, L. (2006) · Acta veterinaria · doi:10.2298/avb0606385k
“It has been shown that CVD patients have increased mitochondrial (mt) DNA damage when compared with healthy controls in both the heart and the aorta (Corral-Debrinski et al.,1991; Corral-Debrinski et al., 1992, Knight-Lozano et al., 2002; Ballinger et al., 2002).”
Background

Authors: Corral-Debrinski, M.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 1991-10-02
Volume: 266
Issue: 13
Pages: 1812
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.1991.03470130092035
OpenAlex: W7214182327
Cited by: 1
References: 0
FWCI: 0.00
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Physiology (medical) › High Altitude and Hypoxia
Keywords: hypoxemia, mitochondrial DNA damage, gene induction, oxidative stress

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Hypoxemia Is Associated With Mitochondrial DNA Damage and Gene Induction: Implications for Cardiac Disease

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