© 2000 American Heart Association, Inc.
Clinical Research |
Increased Expression of Cytoskeletal, Linkage, and Extracellular Proteins in Failing Human Myocardium
From the Department of Experimental Cardiology (A.H., S.K., Y.M., M.S., W.S., J.S.), Max Planck Institute, and Department of Cardiac Surgery (R.Z., S.H., E.B., W.-P.K.), Kerckhoff-Clinic, Bad Nauheim, Germany, and Centre Hospitalier (B.D.), Université de Rouen, France.
Correspondence to Jutta Schaper, MD, Department of Experimental Cardiology, Max-Planck-Institute, Benekestrasse D-61231, Bad Nauheim, Germany. E-mail j.schaper{at}kerckhoff.mpg.de
Abstract—Experimental studies
have shown that in hypertrophy and heart failure,
accumulation of microtubules occurs that impedes sarcomere motion and
contributes to decreased ventricular compliance. We tested
the hypothesis that these changes are present in the failing human
heart and that an entire complex of structural components, including
cytoskeletal, linkage, and extracellular proteins, are involved in
causing functional deterioration. In explanted human hearts failing
because of dilated cardiomyopathy (ejection
fraction 
20%), expression of 
- and ß-tubulin, desmin, vinculin,
fibronectin, and vimentin was determined by Northern and Western blot
analysis and compared with normal myocardium from
explants not used for transplantation. The mRNA for - and
ß-tubulin was increased to 2.4-fold (P<0.01) and
1.25-fold (NS), respectively; for desmin, 1.2-fold
(P<0.05); for fibronectin, 5-fold
(P<0.001); and for vimentin, 1.7-fold
(P<0.05). Protein levels for -tubulin increased
2.6-fold (P<0.02); for ß-tubulin, 1.2-fold
(P<0.005); for desmin, 2.1-fold
(P<0.001); for vinculin, 1.2-fold
(P<0.005); for fibronectin, 2.9-fold
(P<0.001); and for vimentin, 1.5-fold
(P<0.005). Confocal microscopy showed augmentation and
disorganization of all proteins studied. In combination with the loss
of myofilaments and sarcomeric skeleton previously reported, these
changes suggest cardiomyocyte remodeling. Increased
fibronectin and elevated interstitial cellularity (vimentin
labeling) indicate progressive fibrosis. The present results
suggest a causative role of cytoskeletal abnormalities and myofilament
loss for intrinsic contractile and diastolic dysfunction in
failing hearts.
Key Words: heart failure • cardiomyopathy • cytoskeleton • fibrosis • structure
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