Abstract:
AIMS:Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a higher risk of thrombotic events. These effects can be explained by a reduction in free bioavailable nitric oxide that is inactivated by an age-dependent increase in superoxide formation. In the present study, mitochondria as a source of reactive oxygen species (ROS) and the contribution of manganese superoxide dismutase (MnSOD, SOD-2) and aldehyde dehydrogenase (ALDH-2) were investigated. METHODS AND RESULTS:Age-dependent effects on vascular function were determined in aortas of C57/Bl6 wild-type (WT), ALDH-2(-/-), MnSOD(+/+), and MnSOD(+/-) mice by isometric tension measurements in organ chambers. Mitochondrial ROS formation was measured by luminol (L-012)-enhanced chemiluminescence and 2-hydroxyethidium formation with an HPLC-based assay in isolated heart mitochondria. ROS-mediated mitochondrial DNA (mtDNA) damage was detected by a novel and modified version of the fluorescent-detection alkaline DNA unwinding (FADU) assay. Endothelial dysfunction was observed in aged C57/Bl6 WT mice in parallel to increased mitochondrial ROS formation and oxidative mtDNA damage. In contrast, middle-aged ALDH-2(-/-) mice showed a marked vascular dysfunction that was similar in old ALDH-2(-/-) mice suggesting that ALDH-2 exerts age-dependent vasoprotective effects. Aged MnSOD(+/-) mice showed the most pronounced phenotype such as severely impaired vasorelaxation, highest levels of mitochondrial ROS formation and mtDNA damage. CONCLUSION:The correlation between mtROS formation and acetylcholine-dependent relaxation revealed that mitochondrial radical formation significantly contributes to age-dependent endothelial dysfunction.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Wenzel P,Schuhmacher S,Kienhöfer J,Müller J,Hortmann M,Oelze M,Schulz E,Treiber N,Kawamoto T,Scharffetter-Kochanek K,Münzel T,Bürkle A,Bachschmid MM,Daiber Adoi
10.1093/cvr/cvn182subject
Has Abstractpub_date
2008-11-01 00:00:00pages
280-9issue
2eissn
0008-6363issn
1755-3245pii
cvn182journal_volume
80pub_type
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abstract:OBJECTIVE:The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of thi...
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journal_title:Cardiovascular research
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doi:10.1093/cvr/cvaa181
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journal_title:Cardiovascular research
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doi:10.1016/j.cardiores.2006.10.003
更新日期:2007-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00187-5
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doi:10.1093/cvr/cvw095
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更新日期:2013-02-01 00:00:00
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更新日期:2006-09-01 00:00:00
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更新日期:2016-01-01 00:00:00
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doi:10.1016/j.cardiores.2003.12.027
更新日期:2004-04-01 00:00:00
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journal_title:Cardiovascular research
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doi:
更新日期:1995-02-01 00:00:00
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doi:10.1093/cvr/cvu136
更新日期:2014-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2003.12.022
更新日期:2004-04-01 00:00:00
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更新日期:2004-05-01 00:00:00
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doi:10.1093/cvr/23.3.262
更新日期:1989-03-01 00:00:00
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更新日期:2011-01-01 00:00:00
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doi:10.1093/cvr/26.6.603
更新日期:1992-06-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00052-1
更新日期:1996-08-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00498-4
更新日期:2002-10-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.12.1863
更新日期:1994-12-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.12.018
更新日期:2004-03-01 00:00:00
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journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 00:00:00