Document Detail


β-Adrenergic receptor antagonists ameliorate myocyte T-tubule remodeling following myocardial infarction.
MedLine Citation:
PMID:  22375019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
β-Adrenergic receptor (AR) blockers provide substantial clinical benefits, including improving overall survival and left ventricular (LV) function following myocardial infarction (MI), though the mechanisms remain incompletely defined. The transverse-tubule (T-tubule) system of ventricular myocytes is an important determinant of cardiac excitation-contraction function. T-tubule remodeling occurs early during LV failure. We hypothesized that β-AR blockers prevent T-tubule remodeling and thereby provide therapeutic benefits. A murine model of MI was utilized to examine the effect of β-AR blockers on T-tubule remodeling following LV MI. We applied the in situ imaging of T-tubule structure from Langendorff-perfused intact hearts with laser scanning confocal microscopy. We found that MI caused remarkable T-tubule remodeling near the infarction border zone and moderate LV remodeling remote from the MI. Metoprolol and carvedilol administered 6 d after MI for 4 wk each increased the T-tubule integrity at the remote and border zones. At the molecular level, both β-AR blockers restored border and remote zone expression of junctophilin-2 (JP-2), which is involved in T-tubule organization and formation of the T-tubule/sarcoplasmic reticulum junctions. In contrast, β-AR blockers had no significant effects on caveolin-3 expression. In summary, our data show that β-AR antagonists can protect against T-tubule remodeling after MI, suggesting a novel therapeutic mechanism of action for this drug class. Preservation of JP-2 expression may contribute to the beneficial effects of metoprolol and carvedilol on T-tubule remodeling.
Authors:
Biyi Chen; Yue Li; Shuxia Jiang; Yu-Ping Xie; Ang Guo; William Kutschke; Kathy Zimmerman; Robert M Weiss; Francis J Miller; Mark E Anderson; Long-Sheng Song
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-28
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-08-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2531-7     Citation Subset:  IM    
Affiliation:
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology*,  therapeutic use
Animals
Carbazoles / pharmacology
Caveolin 3 / biosynthesis
Male
Membrane Proteins / biosynthesis
Metoprolol / pharmacology
Mice
Myocardial Infarction / drug therapy,  physiopathology*
Myocytes, Cardiac / drug effects*,  physiology*
Propanolamines / pharmacology
Ventricular Remodeling / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
R01 HL090905/HL/NHLBI NIH HHS; RR026293/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Carbazoles; 0/Caveolin 3; 0/Membrane Proteins; 0/Propanolamines; 0/junctophilin; 0K47UL67F2/carvedilol; 37350-58-6/Metoprolol
Comments/Corrections

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


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