Thorac Cardiovasc Surg 2012; 60 - PP138
DOI: 10.1055/s-0031-1297785

In vitro endothelial cell activation after heart transplantation as a biomarker for the development of acute and chronic rejection

J Kroher 1, A Haneya 1, SW Hirt 1, K Lehle 1, C Schmid 1
  • 1Uniklinikum Regensburg, Klinik und Poliklinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Regensburg, Germany

Objective: Increased cell adhesion molecular expression is characteristic for chronic rejection. The aim of the study was to determine if serum from HTX patients possesses a net proinflammatory bioactivity to activate cultured EC.

Methods and materials: Human umbilical vein EC were cultured and then incubated with serum from 34 HTX patients and 38 healthy volunteers. Serum was obtained from transplant patients before and during the 1st year post-HTX. Endothelial surface expression of E-selectin, VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) was studied. Tumor necrosis factor was selected as reference. The threshold for basal expression of adhesion molecules was defined as mean plus 2 x standard deviation of the percentage of TNF-stimulated cells.

Results: Basal expression was 3.9 for E-selectin, 4.6 for VCAM-1, and 3.2 for ICAM-1. Stimulation did no alter the expression of E-selectin, and demonstrated only a small increase in VCAM-1 (factor 1.5±0.6 over threshold, p<0.05) in 6 patients. ICAM-1 expression did not uniformly alter after stimulation. In all but 4 patients (who did not respond!) the expression of ICAM-1 (factor 2.7±1.2 over threshold, p<0.05) increased significantly. The time course of the ICAM-1 slope showed either a steady increase (12 patients: factor 4.9±2.2 over threshold), or 1 to 5 peak values (11 patients: factor 4–10 over threshold). Five patients had already high values pre-HTX (factor 5–8 over threshold) and reached the threshold values after 2 weeks post-HTX. Overall, there was no correlation with clinical rejection episodes.

Conclusions: During the 1st year post-HTX, patients released pro-inflammatory cytokines which can induce or augment expression of EC surface adhesion molecules. As there was a great variability among patients and no correlation with clinical rejection episodes its prognostic value as a marker is unclear.