TNF-related apoptosis-inducing ligand and its decoy receptor osteoprotegerin in nonischemic dilated cardiomyopathy.
Apoptosis has been attributed an essential role in dilated cardiomyopathy (DCM) recently. We assessed expression of TNF-related apoptosis-inducing ligand (TRAIL) and its decoy receptor osteoprotegerin (OPG) in men with nonischemic DCM, who underwent coronary angiography and endomyocardial biopsy (EMB) after exclusion of coronary artery disease compared to control patients. TRAIL plasma concentrations were elevated in DCM (p=0.02 vs. controls), and were positively correlated with left ventricular enddiastolic diameter (r=0.15, p=0.04), whereas OPG plasma levels did not differ between both groups (p=0.96). In EMB of DCM patients, TRAIL and OPG protein were detected by immunohistochemistry but not in controls. Furthermore, gene expression in EMB or peripheral blood leukocytes (PBL) of DCM patients assessed by real-time PCR showed an increase of TRAIL mRNA in PBL (p=0.01 vs. controls), whereas OPG mRNA was upregulated in endomyocardial specimens (p<0.001 vs. controls). In conclusion, myocardial overexpression of antiapoptotic OPG in DCM patients may represent a compensatory mechanism to limit systemic activation of TRAIL in patients with congestive heart disease.
Schoppet
Michael
M
Department of Internal Medicine and Cardiology, Philipps-University, D-35033 Marburg, Germany. schoppet@mailer.uni-marburg.de
Ruppert
Volker
V
Hofbauer
Lorenz C
LC
Henser
Stephanie
S
Al-Fakhri
Nadia
N
Christ
Michael
M
Pankuweit
Sabine
S
Maisch
Bernhard
B
D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D005318:Fetal Heart / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D051017:Apoptosis Regulatory Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C506030:TNFRSF11B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha