Journal article
Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.296(1), pp.R1-R8
Physiological and Molecular Mechanisms Implicated in the Neural Control of Circulation
10/29/2008
DOI: 10.1152/ajpregu.00078.2008
PMCID: PMC2636979
PMID: 18971355
Abstract
Dysregulation in central nervous system (CNS) signaling that results in chronic sympathetic hyperactivity is now recognized to play a critical role in the pathogenesis of heart failure (HF) following myocardial infarction (MI). We recently demonstrated that adenovirus-mediated gene transfer of cytoplasmic superoxide dismutase (Ad-Cu/ZnSOD) to forebrain circumventricular organs, unique sensory structures that lack a blood-brain barrier and link peripheral blood-borne signals to central nervous system cardiovascular circuits, inhibits both the MI-induced activation of these central signaling pathways and the accompanying sympathoexcitation. Here, we tested the hypothesis that this forebrain-targeted reduction in oxidative stress translates into amelioration of the post-MI decline in myocardial function and increase in mortality. Adult C57BL/6 mice underwent left coronary artery ligation or sham surgery along with forebrain-targeted gene transfer of Ad-Cu/ZnSOD or a control vector. The results demonstrate marked MI-induced increases in superoxide radical formation in one of these forebrain regions, the subfornical organ (SFO). Ad-Cu/ZnSOD targeted to this region abolished the increased superoxide levels and led to significantly improved myocardial function compared with control vector-treated mice. This was accompanied by diminished levels of cardiomyocyte apoptosis in the Ad-Cu/ZnSOD but not the control vector-treated group. These effects of superoxide scavenging with Ad-Cu/ZnSOD in the forebrain paralleled increased post-MI survival rates compared with controls. This suggests that oxidative stress in the SFO plays a critical role in the deterioration of cardiac function following MI and underscores the promise of CNS-targeted antioxidant therapy for the treatment of MI-induced HF.
Details
- Title: Subtitle
- Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction
- Creators
- Timothy E. Lindley - Roy J. and Lucille A. Carver College of MedicineDavid W. InfangerMark RishniwYi ZhouMarc F. DoobayRam V. SharmaRobin L. Davisson - Cornell University
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.296(1), pp.R1-R8
- Series
- Physiological and Molecular Mechanisms Implicated in the Neural Control of Circulation
- DOI
- 10.1152/ajpregu.00078.2008
- PMID
- 18971355
- PMCID
- PMC2636979
- NLM abbreviation
- Am J Physiol Regul Integr Comp Physiol
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Publisher
- American Physiological Society
- Language
- English
- Date published
- 10/29/2008
- Academic Unit
- Physician Assistant Studies; Family and Community Medicine; Injury Prevention Research Center
- Record Identifier
- 9984294959602771
Metrics
18 Record Views