β‐Adrenergic receptor antagonists ameliorate myocyte T‐tubule remodeling following myocardial infarction

• Published in: The FASEB journal 2012-06, Vol.26 (6), p.2531-2537
• Main Authors: Chen, Biyi, Li, Yue, Jiang, Shuxia, Xie, Yu‐Ping, Guo, Ang, Kutschke, William, Zimmerman, Kathy, Weiss, Robert M., Miller, Francis J., Anderson, Mark E., Song, Long‐Sheng
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Adrenergic beta-Antagonists - therapeutic use; Animals; Carbazoles - pharmacology; Caveolin 3 - biosynthesis; heart failure; Male; Membrane Proteins - biosynthesis; Metoprolol - pharmacology; Mice; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Propanolamines - pharmacology; Research Communications; Ventricular Remodeling - drug effects; Ventricular Remodeling - physiology; β‐AR blockers
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.11-199505

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. FASEB J. 26, 2531‐2537 (2012). www.fasebj.org