Enhanced expression of the apoptosis inducing ligand TRAIL in mononuclear cells after myocardial infarction.

Abstract

Tumor necrosis factor (TNF) family proteins including TNF-alpha and Fas (CD95)-ligand have been implicated in the development of acute myocardial infarction (AMI). We studied whether AMI patients displayed up-regulation of another TNF family member, TNF-related-apoptosis-inducing ligand (TRAIL), on peripheral blood mononuclear cells (PBMCs). We compared expression of TRAIL on PBMCs from 26 patients in the acute phase of AMI with that on PBMCs from 16 healthy control subjects using flow cytometry and RT-PCR. In addition, expression of TRAIL protein on PBMCs from patients in the acute phase of AMI was also compared with that from the same patients 7 days later. Furthermore, we compared the expression of TRAIL protein on CD4+, CD8+, CD14+, and CD19+ cells from patients in the acute phase of AMI with that from control subjects using flow cytometry. Finally, expression of the TRAIL receptors (TRAILR)-1 and TRAILR-2 in human cardiomyocytes was examined immunohistochemically. Expression of TRAIL protein was significantly higher in the acute phase of AMI than in control subjects. Expression of TRAIL protein was significantly higher in the acute phase of AMI than 7 days later. TRAIL mRNA expression in the acute phase of AMI was higher than in control subjects. Expression of TRAIL protein on CD4+ and CD14+ cells from AMI patients was significantly higher than that from control subjects. Expression of TRAILR-1 and TRAILR-2 in human cardiomyocytes was confirmed immunohistochemically. TRAIL on infiltrating CD4 and CD146 cells may be involved in the induction of cardiomyocyte apoptosis after AMI.