Cardiac hypertrophy, a compensatory mechanism, is characterized by enlargement of individual cardiac myocytes. The enlargement, which does not compromise ventricular function, occurs in response to increased workload. The heart progresses into a stage known as heart failure. In this stage of heart failure ventricular function is severely compromised. In some patients who require a heart transplant for end stage heart failure, a left ventricular assist device (LVAD) is implanted into the heart to mechanically unload the left ventricle.; Two factors which contribute to contractile dysfunction in the failing heart include impaired calcium cycling via excitation-contraction coupling and decreased β-adrenergic responsiveness. In addition, structural alterations such as increased cell size and increased fibrosis may occur and contribute to decreased contractile function. Alterations in the cytoskeleton, a network of proteins which maintains the structure of the cardiac myocyte, may also play a role in heart failure.; Quantitation of cytoskeletal proteins by Western blot analysis was used to test the hypothesis that the cytoskeletal proteins, α-actinin, vinculin, desmin and β-tubulin, are altered in human heart failure and to a lesser degree in cardiac hypertrophy. The localization of these proteins was examined in isolated human cardiac myocytes from nonfailing, hypertrophied and failing hearts by immunofluorescence using confocal microscopy. Similarly, the effects of reversibility by mechanical unloading with an LVAD were also tested. The effect of depolymerization and hyperpolymerization of β-tubulin on the β-adrenergic response was also tested using muscles from failing hearts.; There were no significant differences in α-actinin, vinculin and β-tubulin protein in hypertrophied and failing hearts as compared to nonfailing hearts. However, there was a significant increase in desmin protein. Immunofluorescence revealed alterations in the localization of vinculin, desmin and β-tubulin in hypertrophied and failing cardiac myocytes. The functional effect of increased β-tubulin polymerization on the β-adrenergic response was negligible. This study has shown that cytoskeletal proteins, although not quantitatively altered, are qualitatively changed in the hypertrophied and failing human heart. Functional implications of these changes remain to be clarified.
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