Preferential Existence of Death-Inducing Proteins in the Human Cardiomyopathic Left Ventricle

Introduction

Idiopathic or acquired dilated cardiomyopathy (DCM) is a leading health threat resulting in considerable mortality and serious long-term disability with a substantial economic healthcare expenditure. The purpose of this study was to investigate the modulation of apoptotic signaling genes in human cardiomyopathy.

Methods

Cardiac tissue was obtained from six heart transplant recipients (age = 43 ± 7 y) with DCM. Equivalent control specimens were taken from six healthy heart donors (age = 33 ± 4 y). The mRNA expression of death-inducing proteins, the death (DRs) and decoy receptors (DcRs), in the four cardiac chambers was quantified using real time polymerase chain reaction LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). Immunodetectable receptor protein expression was quantified densitometrically. Data were analyzed by analysis of variance and unpaired Student’s t-test.

Results

In DCM tissues, DR1 mRNA was elevated by 42.7% (P < 0.01) in the left ventricle (LV) and 56.4% (P < 0.001) in the left atrium (LA), while DR2 increased by 112.5% (P < 0.00001) in LV and 45.8% (P < 0.05) in LA. Increase in DR4 was 29.6% (P < 0.01) in LV, 82.5% (P < 0.01) in the right ventricle (RV), 210.8% (P < 0.01) in LA, and 99.1% (P < 0.01) in the right atrium (RA). DR5 was elevated by 66.7% (P < 0.01) in LV, 181.8% (P < 0.005) in LA, and 90.2% (P < 0.05) in RA. DcR1 decreased by 30.8% in LV, 44% (P < 0.05) in LA, and 12.5% in RA; DcR3 by 67.1% (P < 0.0001) in LV, 82.4% (P < 0.0001) in RV, 85.1% (P < 0.0001) in LA, and 84.6% (P < 0.0001) in RA. The trends in mRNA expression were comparable to the changes in protein expression.

Conclusions

Left heart-sided increase of death-inducing proteins in human cardiomyopathy is suggestive of their potential modulatory roles in death-related signaling in the pathogenesis of end-stage myocardial failure.

Key Words: apoptosis, cell survival/death signaling, death receptors