| Mitochondrial targeted antioxidant Peptide ameliorates hypertensive cardiomyopathy. | |
| | |
MedLine Citation:
|
PMID: 21620606 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVES: We investigated the effect of reducing mitochondrial oxidative stress by the mitochondrial-targeted antioxidant peptide SS-31 in hypertensive cardiomyopathy. BACKGROUND: Oxidative stress has been implicated in hypertensive cardiovascular diseases. Mitochondria and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase have been proposed as primary sites of reactive oxygen species (ROS) generation. METHODS: The mitochondrial targeted antioxidant peptide SS-31 was used to determine the role of mitochondrial oxidative stress in angiotensin II (Ang)-induced cardiomyopathy as well as in Gαq overexpressing mice with heart failure. RESULTS: Ang induces mitochondrial ROS in neonatal cardiomyocytes, which is prevented by SS-31, but not the nontargeted antioxidant N-acetyl cysteine (NAC). Continuous administration of Ang for 4 weeks in mice significantly increased both systolic and diastolic blood pressure, and this was not affected by SS-31 treatment. Ang was associated with up-regulation of NADPH oxidase 4 (NOX4) expression and increased cardiac mitochondrial protein oxidative damage, and induced the signaling for mitochondrial biogenesis. Reducing mitochondrial ROS by SS-31 substantially attenuated Ang-induced NOX4 up-regulation, mitochondrial oxidative damage, up-regulation of mitochondrial biogenesis, and phosphorylation of p38 mitogen-activated protein kinase and prevented apoptosis, concomitant with amelioration of Ang-induced cardiac hypertrophy, diastolic dysfunction, and fibrosis, despite the absence of blood pressure-lowering effect. The NAC did not show any beneficial effect. The SS-31 administration for 4 weeks also partially rescued the heart failure phenotype of Gαq overexpressing mice. CONCLUSIONS: Mitochondrial targeted peptide SS-31 ameliorates cardiomyopathy resulting from prolonged Ang stimulation as well as Gαq overexpression, suggesting its potential clinical application for target organ protection in hypertensive cardiovascular diseases. |
| | |
Authors:
|
Dao-Fu Dai; Tony Chen; Hazel Szeto; Madeline Nieves-Cintrón; Vassily Kutyavin; Luis F Santana; Peter S Rabinovitch |
Related Documents
:
|
8694316 - Effect of oncotic pressure of diaspirin cross-linked hemoglobin (dclhb) on brain injury... 8696746 - Experimental application of controlled limb reperfusion after incomplete ischaemia. 10865046 - Effect of ischemia/reperfusion as a systemic phenomenon on anastomotic healing in the l... 7397996 - Regional myocardial protection: use of a new method to compare cold potassium cardiople... 6221856 - Cardiac muscle mass during vasodilation therapy of hypertension. 12386506 - Lithium dilution measurement of cardiac output and arterial pulse waveform analysis: an... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-05-27 |
Journal Detail:
|
Title: Journal of the American College of Cardiology Volume: 58 ISSN: 1558-3597 ISO Abbreviation: J. Am. Coll. Cardiol. Publication Date: 2011 Jun |
Date Detail:
|
Created Date: 2011-06-24 Completed Date: 2011-08-24 Revised Date: 2012-05-10 |
Medline Journal Info:
|
Nlm Unique ID: 8301365 Medline TA: J Am Coll Cardiol Country: United States |
Other Details:
|
Languages: eng Pagination: 73-82 Citation Subset: AIM; IM |
Copyright Information:
|
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Pathology, University of Washington, 1959 Pacific Avenue Northeast, Seattle, WA 98195, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antioxidants / metabolism* Apoptosis MAP Kinase Signaling System Mice Mitochondria / metabolism* Myocytes, Cardiac / cytology NADPH Oxidase / metabolism Oligopeptides / metabolism* Oxidative Stress Peptides / chemistry* Phenotype Reactive Oxygen Species Signal Transduction Up-Regulation p38 Mitogen-Activated Protein Kinases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
P01 AG001751/AG/NIA NIH HHS; P01 AG001751/AG/NIA NIH HHS; P01 AG001751-28A1/AG/NIA NIH HHS; P01 AG001751-29/AG/NIA NIH HHS; P30 AG013280/AG/NIA NIH HHS; P30 AG013280/AG/NIA NIH HHS; P30 AG013280-17/AG/NIA NIH HHS; P30 AG013280-18/AG/NIA NIH HHS; R01 HL101186/HL/NHLBI NIH HHS; R01 HL101186/HL/NHLBI NIH HHS; R01 HL101186-01/HL/NHLBI NIH HHS; R01 HL101186-02/HL/NHLBI NIH HHS; R01 HL101186-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antioxidants; 0/Oligopeptides; 0/Peptides; 0/Reactive Oxygen Species; 0/arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; EC 1.6.3.1/NADPH Oxidase; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases |
| Comments/Corrections | |
Comment In:
|
J Am Coll Cardiol. 2011 Jun 28;58(1):83-6
[PMID:
21620605
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effect of the traditional Chinese medicine tongxinluo on endothelial dysfunction rats studied by usi...
Next Document: Humerus Axial Traction with Acromial Fixation Reduction Maneuver for Anterior Shoulder Dislocation.