Journal article
β-Adrenergic receptor antagonists ameliorate myocyte T-tubule remodeling following myocardial infarction
The FASEB journal, Vol.26(6), pp.2531-2537
06/2012
DOI: 10.1096/fj.11-199505
PMCID: PMC3360148
PMID: 22375019
Abstract
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.—Chen, B., Li, Y., Jiang, S., Xie, Y.-P., Guo, A., Kutschke, W., Zimmerman, K., Weiss, R. M., Miller, F. J., Anderson, M. E., Song, L.-S. β-Adrenergic receptor antagonists ameliorate myocyte T-tubule remodeling following myocardial infarction.
Details
- Title: Subtitle
- β-Adrenergic receptor antagonists ameliorate myocyte T-tubule remodeling following myocardial infarction
- Creators
- Biyi Chen - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andYue Li - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andShuxia Jiang - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andYu-Ping Xie - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andAng Guo - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andWilliam Kutschke - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andKathy Zimmerman - Department of Veterans Affairs Medical Center, Iowa City, Iowa, USARobert M Weiss - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andFrancis J Miller - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andMark E Anderson - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; andLong-Sheng Song - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine; Iowa City, Iowa, USA; and
- Resource Type
- Journal article
- Publication Details
- The FASEB journal, Vol.26(6), pp.2531-2537
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fj.11-199505
- PMID
- 22375019
- PMCID
- PMC3360148
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: NIH R01 HL090905, RR026293; DOI: 10.13039/100000968, name: American Heart Association, award: 11POST7640011
- Language
- English
- Date published
- 06/2012
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984094659002771
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