Chronic pressure overload cardiac hypertrophy and failure in guinea pigs: II. Cytoskeletal remodeling.
The cytoskeleton is a major regulator of cell shape. To explore potential mechanisms for maladaptation of cardiac myocyte shape in pressure overload-induced congestive heart failure, the abundance and organization of major intra- and extra-myofibrillar cytoskeleton of cardiac myocytes were examined with western blotting and confocal microscopy in guinea pigs with chronic aortic stenosis. It was found that: (1) the amount and distribution of alpha-actinin and myomesin remained unchanged at both the compensated hypertrophy and the congestive heart failure stages; (2) loss of titin was associated with myocyte lengthening in heart failure; (3) desmin protein and filaments in LV myocytes increased progressively with mechanical overload cardiac hypertrophy and subsequent heart failure; (4) a newly developed and validated quantitative confocal microscopic approach disclosed that the microtubule density in isolated LV myocytes increased by 21% at 4 weeks and by 48% 6 months after aortic constriction; (5) at the heart failure stage, microtubule density in LV myocytes showed a statistically significant inverse correlation to the LV maximum +dP/dt and a direct correlation to LV myocyte lengthening; (6) the increased microtubule density in LV myocytes in this model was not due to an increase in total tubulin; and (7) microtubule density in left atrial and right ventricular myocytes also increased when they underwent hypertrophy secondary to left heart failure. These results suggest that the down-regulation of titin and up-regulation of microtubule and desmin filaments may contribute to myocyte lengthening and malfunction in pressure overload congestive heart failure.
Wang
X
X
South Dakota Health Research Foundation Cardiovascular Research Institute, Sioux Falls 57105, USA.
Li
F
F
Campbell
S E
SE
Gerdes
A M
AM
D000185:Actinin / Q000378:metabolism; D000818:Animals; D064211:Connectin; D003599:Cytoskeleton / Q000648:ultrastructure; D003893:Desmin / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D018613:Microscopy, Confocal; D008870:Microtubules; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000166:cytology; D017725:Ventricular Pressure / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
D064211:Connectin; D003893:Desmin; D009124:Muscle Proteins; D000185:Actinin