Document Detail


Hypertensive hypertrophied myocardium is vulnerable to infarction and refractory to erythropoietin-induced protection.
MedLine Citation:
PMID:  21060000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this study was to examine the hypothesis that hypertensive hypertrophy is vulnerable to infarction and defective in cytoprotective mechanisms by modification of intracellular signaling and mitochondrial proteins. Myocardial infarction was induced by 20-minute coronary occlusion/reperfusion in spontaneously hypertensive stroke-prone rats (SHR-SPs) and their controls (Wistar-Kyoto rats [WKYs]). Infarct size expressed as a percentage of area-at-risk was larger by 29% in SHR-SPs than in WKYs. Pretreatment with erythropoietin (EPO) significantly limited infarct size in WKYs but not in SHR-SPs. Ca(2+) retention capacity of mitochondria, an index of the threshold for opening of the mitochondrial permeability transition pore, on reperfusion was reduced in SHR-SPs compared with that in WKYs. Suppression of reactive oxygen species by N-(2-mercaptopropionyl)-glycine increased Ca(2+) retention capacity after reperfusion and limited infarct size in SHR-SPs to levels in WKYs. EPO induced phosphorylation of Akt, extracellular signal-related kinase, and glycogen synthase kinase-3β in the myocardium in both WKYs and SHR-SPs. EPO enhanced interaction of phospho-glycogen synthase kinase-3β and adenine nucleotide translocase on reperfusion in WKYs, although such an effect of EPO was not detected in SHR-SPs. The results suggest that enhanced opening of mitochondrial permeability transition pores by reactive oxygen species and modification of the signal downstream of phospho-glycogen synthase kinase-3β in the mitochondria underlie the increased vulnerability to infarction and the lack of anti-infarct tolerance by EPO, respectively, in hypertensive hypertrophied hearts.
Authors:
Toshiyuki Yano; Takayuki Miki; Masaya Tanno; Atsushi Kuno; Takahito Itoh; Akifumi Takada; Tatsuya Sato; Hidemichi Kouzu; Kazuaki Shimamoto; Tetsuji Miura
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-08
Journal Detail:
Title:  Hypertension     Volume:  57     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-16     Completed Date:  2011-01-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  110-5     Citation Subset:  IM    
Affiliation:
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium / analysis
Cardiomegaly / etiology*
Erythropoietin / therapeutic use*
Hypertension / complications*
Male
Mitochondria, Heart / drug effects,  enzymology,  metabolism
Mitochondrial ADP, ATP Translocases / analysis
Mitochondrial Membrane Transport Proteins / drug effects
Myocardial Infarction / etiology*,  prevention & control*
Myocardium / enzymology
Protein-Serine-Threonine Kinases / analysis
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Reactive Oxygen Species / antagonists & inhibitors
Risk Factors
Tiopronin / pharmacology
Chemical
Reg. No./Substance:
0/Mitochondrial Membrane Transport Proteins; 0/Reactive Oxygen Species; 0/mitochondrial permeability transition pore; 11096-26-7/Erythropoietin; 1953-02-2/Tiopronin; 7440-70-2/Calcium; 9068-80-8/Mitochondrial ADP, ATP Translocases; EC 2.7.11.1/Protein-Serine-Threonine Kinases

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


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