Quantitative analysis of apoptotic markers in human end-stage heart failure.
Apoptosis--programmed cell death--has been implicated in a variety of cardiac diseases, including myocardial infarction and chronic heart failure. This study was conducted to quantify the amount of apoptotic markers in human end-stage heart failure and to correlate the results to clinical parameters of heart failure. Myocardial samples from 44 patients with end-stage heart failure and 5 controls were collected at the time of heart transplantation. Lysates of tissue samples were analysed for cleavage of alpha actin, alpha actinin, troponin T, tropomyosin, essential myosin light chain-1 (MLC-1v), and gelsolin. We observed cleavage of alpha actin, and alpha actinin. Troponin I, tropomyosin, and MLC-1v were not detectably cleaved. The amount of active caspase-3 was low in all samples (1.10+/-0.1 ng/ml). The same applied for DNA histone fragments (0.61+/-0.04). In patients with acutely decompensated heart failure we observed a striking increase in caspase-3 activity, but not DNA fragmentation. When calculated for the entire group there was no correlation between caspase-3 activity, DNA fragmentation and haemodynamic or echocardiographic variables. Relevant increases in apoptosis were only observed in patients with acute decompensated heart failure.
Bott-Flügel
Lorenz
L
Medizinische Klinik und Deutsches Herzzentrum München, Technische Universität, Munich, Germany. bott-fluegel@med1.med.tu-muenchen.de
Weig
Hans-Jörg
HJ
Uhlein
Heiko
H
Nabauer
Michael
M
Laugwitz
Karl-Ludwig
KL
Seyfarth
Melchior
M
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D002311:Cardiomyopathy, Dilated / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism*; D002908:Chronic Disease; D053837:DNA Cleavage; D053938:DNA Fragmentation; D005260:Female; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D014335:Tropomyosin / Q000378:metabolism; D019210:Troponin I / Q000378:metabolism
D000199:Actins; C425069:MLC1 protein, human; D008565:Membrane Proteins; D014335:Tropomyosin; D019210:Troponin I; D000185:Actinin; D053148:Caspase 3