Chronic pressure overload cardiac hypertrophy and failure in guinea pigs

III. Intercalated disc remodeling

Xuejun Wang, A. Martin Gerdes

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The intercalated disc is an extremely important specialised structure of cardiac muscle. Intercalated disc alterations have been implicated in ischemic and dilated cardiomyopathy. With a chronic aortic stenosis guinea pig model, we demonstrated in the current study substantial intercalated disc remodeling during the progression of compensated left ventricular (LV) hypertrophy to congestive left heart failure. For the first time, we reported that although the abundance of β-catenin and vinculin remained unchanged as shown by quantitative Western blotting, the normal distribution of β-catenin and vinculin at intercalated disc sites was relocated into the cell body in a large fraction of LV myocytes. γ-Catenin did not show a compensatory up-regulation at the intercalated disc sites where β-catenin concentration was reduced. Both abundance and distribution of the transmembrane protein N-cadherin remained unchanged in this model. While co-labeled N-cadherin remained unchanged, quantitative confocal microscopy shows that the amount of connexin43 per LV myocyte decreased by 37% at the congestive heart failure stage but not at the compensated hypertrophy stage. No compensatory upregulation of connexin45 was evident when connexin43 was decreased in failing LV myocytes. The relocation of β-catenin and vinculin away from intercalated discs in failing myocytes may impair the mechanical linkage between N-cadherin and thin filaments and adversely affect myocyte shape. Loss of connexin43 in LV myocytes may impair electrical coupling of adjacent myocytes.

Original languageEnglish (US)
Pages (from-to)333-343
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume31
Issue number2
DOIs
StatePublished - Jan 1 1999

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Cardiomegaly
Muscle Cells
Catenins
Guinea Pigs
Heart Failure
Pressure
Vinculin
Connexin 43
Cadherins
Up-Regulation
Normal Distribution
Aortic Valve Stenosis
Dilated Cardiomyopathy
Left Ventricular Hypertrophy
Confocal Microscopy
Hypertrophy
Myocardium
Western Blotting
Proteins

Keywords

  • Cadherin
  • Cardiac myocytes
  • Catenins
  • Connexins
  • Desmoplakin
  • Intercalated discs
  • Pressure overload
  • Vinculin

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Chronic pressure overload cardiac hypertrophy and failure in guinea pigs : III. Intercalated disc remodeling. / Wang, Xuejun; Gerdes, A. Martin.

In: Journal of Molecular and Cellular Cardiology, Vol. 31, No. 2, 01.01.1999, p. 333-343.

Research output: Contribution to journalArticle

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