title: Myocardial gene expression of regulators of myocyte apoptosis and myocyte calcium homeostasis during hemodynamic unloading by ventricular assist devices in patients with end-stage heart failure.
abstract: BACKGROUND
  In patients with end-stage heart failure, characterized by an increased susceptibility to cardiomyocyte apoptosis and a labile cardiomyocyte calcium homeostasis, a ventricular assist device (VAD) is implanted for bridging to cardiac transplantation and results in myocardial unloading. Although phenotype changes in the failing heart are assumed to result from hemodynamic overload, the reversibility of these changes under unloading is unknown.
  
  
  RESULTS
  By use of quantitative reverse-transcription polymerase chain reaction, mRNA expression analyses were performed on left ventricular specimens obtained from 10 nonfailing donor hearts (from 8 patients with dilated cardiomyopathy and 2 patients with coronary heart disease) at the time of VAD implantation and 36 to 169 days later during VAD removal with subsequent cardiac transplantation. In terminally failing hearts before VAD support, left ventricular mRNA analyses revealed increased Pro-ANP, reduced antiapoptotic Bcl-x(L) and antiapoptotic Fas isoform FasExo6Del, and a decreased ratio of sarcoplasmic reticulum Ca(2+)-ATPase per sarcolemmal Na(+)-Ca(2+) exchanger in comparison with nonfailing ventricles. After VAD unloading, ventricular transcription of Pro-ANP was immediately normalized, and apoptotic DNA fragmentation was attenuated. In patients with dilated cardiomyopathy, mRNAs of Bcl-x(L) and FasExo6Del/Fas were enhanced depending on time on VAD. The Bcl-x(L) mRNA level correlated positively with that of the Bcl-x(L) protein. Transcription of sarcoplasmic reticulum Ca(2+)-ATPase/Na(+)-Ca(2+) exchanger demonstrated recovery in only 4 of 10 patients.
  
  
  CONCLUSIONS
  Mechanical support of the failing heart induces a time-dependent change in myocardial gene expression compatible with a decreased susceptibility to apoptosis.
authors.affiliation: Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany. babett.bartling@medizin.uni-halle.de
authors.forename: B
authors.initials: B
authors.lastname: Bartling
authors.forename: H
authors.initials: H
authors.lastname: Milting
authors.forename: H
authors.initials: H
authors.lastname: Schumann
authors.forename: D
authors.initials: D
authors.lastname: Darmer
authors.forename: L
authors.initials: L
authors.lastname: Arusoglu
authors.forename: M M
authors.initials: MM
authors.lastname: Koerner
authors.forename: A
authors.initials: A
authors.lastname: El-Banayosy
authors.forename: R
authors.initials: R
authors.lastname: Koerfer
authors.forename: J
authors.initials: J
authors.lastname: Holtz
authors.forename: H R
authors.initials: HR
authors.lastname: Zerkowski
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002118:Calcium / Q000502:physiology*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006352:Heart Ventricles / Q000473:pathology* / Q000503:physiopathology*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D016277:Ventricular Function, Left
chemical_list: D002118:Calcium