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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, B; Li, Y; Jiang, S; Xie, Y-P; Guo, A; Kutschke, W; Zimmerman, K; Weiss, RM; Miller, FJ; Anderson, ME; Song, L-S

Published Date

  • June 2012

Published In

Volume / Issue

  • 26 / 6

Start / End Page

  • 2531 - 2537

PubMed ID

  • 22375019

Pubmed Central ID

  • 22375019

Electronic International Standard Serial Number (EISSN)

  • 1530-6860

Digital Object Identifier (DOI)

  • 10.1096/fj.11-199505

Language

  • eng

Conference Location

  • United States