Document Detail


T-tubule remodeling during transition from hypertrophy to heart failure.
MedLine Citation:
PMID:  20576937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: The transverse tubule (T-tubule) system is the ultrastructural substrate for excitation-contraction coupling in ventricular myocytes; T-tubule disorganization and loss are linked to decreased contractility in end stage heart failure (HF).
OBJECTIVE: We sought to examine (1) whether pathological T-tubule remodeling occurs early in compensated hypertrophy and, if so, how it evolves during the transition from hypertrophy to HF; and (2) the role of junctophilin-2 in T-tubule remodeling.
METHODS AND RESULTS: We investigated T-tubule remodeling in relation to ventricular function during HF progression using state-of-the-art confocal imaging of T-tubules in intact hearts, using a thoracic aortic banding rat HF model. We developed a quantitative T-tubule power (TT(power)) index to represent the integrity of T-tubule structure. We found that discrete local loss and global reorganization of the T-tubule system (leftward shift of TT(power) histogram) started early in compensated hypertrophy in left ventricular (LV) myocytes, before LV dysfunction, as detected by echocardiography. With progression from compensated hypertrophy to early and late HF, T-tubule remodeling spread from the LV to the right ventricle, and TT(power) histograms of both ventricles gradually shifted leftward. The mean LV TT(power) showed a strong correlation with ejection fraction and heart weight to body weight ratio. Over the progression to HF, we observed a gradual reduction in the expression of a junctophilin protein (JP-2) implicated in the formation of T-tubule/sarcoplasmic reticulum junctions. Furthermore, we found that JP-2 knockdown by gene silencing reduced T-tubule structure integrity in cultured adult ventricular myocytes.
CONCLUSIONS: T-tubule remodeling in response to thoracic aortic banding stress begins before echocardiographically detectable LV dysfunction and progresses over the development of overt structural heart disease. LV T-tubule remodeling is closely associated with the severity of cardiac hypertrophy and predicts LV function. Thus, T-tubule remodeling may constitute a key mechanism underlying the transition from compensated hypertrophy to HF.
Authors:
Sheng Wei; Ang Guo; Biyi Chen; William Kutschke; Yu-Ping Xie; Kathy Zimmerman; Robert M Weiss; Mark E Anderson; Heping Cheng; Long-Sheng Song
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-24
Journal Detail:
Title:  Circulation research     Volume:  107     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-09-16     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  520-31     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta, Thoracic / pathology,  physiopathology
Disease Progression
Excitation Contraction Coupling / physiology
Heart Failure / pathology,  physiopathology*
Hypertrophy, Left Ventricular / pathology,  physiopathology*
Male
Microscopy, Confocal
Microtubules / pathology*,  physiology,  ultrastructure
Rats
Rats, Sprague-Dawley
Ventricular Remodeling / physiology*
Grant Support
ID/Acronym/Agency:
R01 HL070250/HL/NHLBI NIH HHS; R01 HL079031/HL/NHLBI NIH HHS; R01 HL090905/HL/NHLBI NIH HHS; R01 HL090905/HL/NHLBI NIH HHS; R01 HL090905-01/HL/NHLBI NIH HHS; R01 HL090905-02/HL/NHLBI NIH HHS; R01 HL090905-02S1/HL/NHLBI NIH HHS; R01 HL090905-03/HL/NHLBI NIH HHS; R01 HL090905-04/HL/NHLBI NIH HHS; R01 HL096652/HL/NHLBI NIH HHS
Comments/Corrections
Comment In:
Future Cardiol. 2011 Jan;7(1):39-42   [PMID:  21174508 ]

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