Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: III. Intercalated disc remodeling.
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 beta-catenin and vinculin remained unchanged as shown by quantitative Western blotting, the normal distribution of beta-catenin and vinculin at intercalated disc sites was relocated into the cell body in a large fraction of LV myocytes. gamma-Catenin did not show a compensatory up-regulation at the intercalated disc sites where beta-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 beta-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.
Wang
X
X
South Dakota Health Research Foundation Cardiovascular Research Institute, Sioux Falls 57105, USA.
Gerdes
A M
AM
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D015534:Trans-Activators; D017725:Ventricular Pressure / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*; D016596:Vinculin / Q000378:metabolism; D051176:beta Catenin; D051185:gamma Catenin
D015820:Cadherins; D017630:Connexins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D016596:Vinculin