Dedifferentiated cardiomyocytes from chronic hibernating myocardium are ischemia-tolerant.
Left ventricular biopsies from 21 patients with clinically diagnosed chronic hibernating myocardium (CHM) were examined by light- and electron microscopy. A mean of 27% of cardiomyocytes were structurally altered and were characterized as hibernating, because of reduced amount of myofibrils and increased glycogen content. Electron microscopy of these cells showed reduction of T-tubules and numerous small mitochondria, but few changes associated with degeneration, acute ischemia or apoptosis. The structural changes found in CHM are reminiscent of dedifferentiation rather than degeneration. The expression patterns of some structural proteins show resemblance with those in embryonic cardiomyocytes. Histochemically, mitochondrial NADH-oxidase and proton translocating ATPase activities were absent, whereas cytochrome c activity was present. Intracellular calcium distribution indicated normally bound sarcolemmal calcium and absence of excess mitochondrial calcium accumulation. Nuclear chromatin ranged from normal to dispersed with only a few nuclei that were clumped. These results suggest that cardiomyocytes from human CHM hearts are structurally altered, but viable, and lack morphologic and cytochemical characteristics suggestive of apoptosis or acute ischemia.
Department of Molecular Cell Biology and Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
J
J
Ausma
F
F
Thoné
G D
GD
Dispersyn
W
W
Flameng
J L
JL
Vanoverschelde
F C
FC
Ramaekers
M
M
Borgers
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000648:ultrastructure; D003576:Electron Transport Complex IV / Q000378:metabolism; D006605:Hibernation; D006801:Humans; D008854:Microscopy, Electron; D009097:Multienzyme Complexes / Q000378:metabolism; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000473:pathology* / Q000503:physiopathology*
D009097:Multienzyme Complexes; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D002118:Calcium