Age-dependent myocardial reinduction of apoptosis inhibitors under VAD in heart failure.
Hemodynamic unloading using the ventricular assist device [VAD] results in partial functional recovery of failing hearts that show increased susceptibility to cardiomyocyte apoptosis. The caspase cascade is the central element of the apoptotic process in cells. We therefore tested expression shifts of left ventricular mRNA of caspases and their endogenous inhibitors from 15 patients with VAD support and successful bridging to transplantation using semiquantitative RT-PCR. Cardiac unloading was shown by the reduction in ventricular Pro-ANP mRNA under VAD. No alteration of mRNA expression under VAD could be observed for initiator caspases, for their selective inhibitors or for apoptotic signal molecules from the mitochondrial intermembrane space. Only two unselective cardiac IAPs (inhibitor of apoptosis protein) were increased under VAD with better recovery in younger patients. In conclusion, our findings indicate that successful hemodynamic unloading by VAD support causes only minor, age-dependent recovery in the expression of IAPs, while presumed alterations in antiapoptotic modulator systems upstream of the caspase cascade still remain to be identified.
Scheubel
R J
RJ
Clinic for Cardiothoracic Surgery, Martin Luther University of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany. robert.scheubel@medizin.uni-halle.de
Bartling
B
B
Stein
S
S
Darmer
D
D
Holtz
J
J
Pregla
R
R
Hetzer
R
R
Koerfer
R
R
Zerkowski
H R
HR
Silber
R E
RE
D000367:Age Factors; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology*; D006353:Heart-Assist Devices; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000502:physiology*
D061945:Caspase Inhibitors; D012333:RNA, Messenger; D020169:Caspases