Document Detail


Decreased FKBP12.6 expression and enhanced endothelin receptor signaling associated with arrhymogenesis in myocardial infarction rats.
MedLine Citation:
PMID:  18570278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An increased propensity towards cardiac arrhythmias and aggravated heart function is observed in myocardial infarction (MI), the development of which is associated with the calcium handling system in the myocardium. It was hypothesized that the abnormal changes in the MI model may be a consequence of the abnormal expression and function of the RyR2-FKBP12.6 channel complex and that these abnormalities may be related to an over-activated endothelin (ET) system. Salvianolic acid B is expected to suppress life-threatening arrhythmias and to restore the abnormality of the RyR2-FKBP12.6 complex in rats. MI was produced by ligating the coronary artery for 4 weeks. Salvianolic acid B (100 mg/kg/day, p.o. for 4 weeks) was administered to rats 0.5 h before surgery. Measurements of cardiac arrhythmias, cardiac function, calcium transient, cardiac calcium release channel handling proteins and the endothelin system were conducted. The aggravated arrhythmia and compromised cardiac function in MI rats was accompanied by elevated diastolic Ca(2+) levels in the cytosol and a significant down-regulation of expression of RyR2-FKBP12.6. These were closely linked with an over-activated ET pathway in the myocardium. After a 4-week treatment with salvianolic acid B, all abnormalities were reversed significantly. Salvianolic acid B was capable of normalizing FKBP12.6 expression levels and decreasing the propensity towards arrhythmias by attenuating the up-regulated ET pathway.
Authors:
Haibo He; Mengqiong Shi; Xiaowei Zeng; Xianzhe Yang; Jun Yang; Limao Wu; Lianda Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Retracted Publication    
Journal Detail:
Title:  Phytotherapy research : PTR     Volume:  22     ISSN:  1099-1573     ISO Abbreviation:  Phytother Res     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-05     Completed Date:  2008-10-02     Revised Date:  2009-01-28    
Medline Journal Info:
Nlm Unique ID:  8904486     Medline TA:  Phytother Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  1115-24     Citation Subset:  IM    
Affiliation:
Institute of Chinese Herb Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, PRC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arrhythmias, Cardiac / drug therapy,  metabolism*,  physiopathology
Benzofurans / therapeutic use*
Calcium / metabolism
Disease Models, Animal
Drugs, Chinese Herbal / therapeutic use*
Gene Expression / drug effects
Hemodynamics / drug effects
Male
Myocardial Infarction / drug therapy,  metabolism*,  physiopathology
Myocardial Reperfusion Injury / drug therapy,  metabolism,  physiopathology
Myocytes, Cardiac / drug effects,  metabolism
Rats
Rats, Sprague-Dawley
Receptors, Endothelin / metabolism*
Ryanodine Receptor Calcium Release Channel / genetics,  metabolism
Signal Transduction
Tacrolimus Binding Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Benzofurans; 0/Drugs, Chinese Herbal; 0/Receptors, Endothelin; 0/Ryanodine Receptor Calcium Release Channel; 115939-25-8/salvianolic acid B; 7440-70-2/Calcium; EC 5.2.1.-/Tacrolimus Binding Proteins; EC 5.2.1.-/tacrolimus binding protein 1B
Comments/Corrections
Retraction In:
Coats A, Williamson EM. Phytother Res. 2008 Dec;22(12):1698   [PMID:  19067374 ]

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


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