Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy.
This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.
Schaper
J
J
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research, Nauheim, FRG.
Froede
R
R
Hein
S
S
Buck
A
A
Hashizume
H
H
Speiser
B
B
Friedl
A
A
Bleese
N
N
D000911:Antibodies, Monoclonal; D002311:Cardiomyopathy, Dilated / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D003599:Cytoskeleton / Q000648:ultrastructure*; D005260:Female; D005455:Fluorescent Antibody Technique; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins