Altered levels of mRNA of apoptosis-mediating genes after mid-term mechanical ventricular support in dilative cardiomyopathy - First results of the Halle Assist Induced Recovery study (HAIR)

Background: Ventricular assist devices (VADs) lead to an immediate unloadin g of the failing heart. Although VADs are used as a bridge to transplant, i n some cases patients suffering from dilated cardiomyopathy have been weane d from the VAD without transplantation after a recovery process initiated b y the cardiac support. Myocardial apoptosis is associated wich inadequate m yocardium and might be reverted during VAD support of the failing heart. Th erefore we measured transcription of apoptosis-associated genes FasExo6 Del , Fas-receptor, and Bcl-x(L) as markers of a putative recovery. Methods: Fa s-receptor, its soluble isoform FasExo6 Del, and Bcl-x(L) mRNA were quantif ied by standard calibrated competitive reverse-transcription polymerase cha in reaction (PCR) in 6 patients suffering from dilated cardiomyopathy. RNA standards were prepared by introducing 100 bp deletions into the native cDN A, resulting in truncated PCR products with identical primer-binding sites. Standards were transcribed in vitro and the resulting RNA was quantified. Results: Transcription of apoptosis-inhibiting genes FasExo6 Del and Bcl-x( L) were upregulated in patients supported for more than 6 weeks. Fas recept or mRNA remained unaffected by VAD support. Conclusions: Transcriptional up regulation of apoptosis-inhibiting genes might be caused by a desensitizati on to apoptotic stimuli and might indicate a relaxation of the diseased sta tus of the myocardium. These data outline the first biochemical evidence of a remodelling process occurring in supported ventricular myocardium.