Abstract 11717: Expression of Tumor Endothelial Marker 1 in Cardiac Fibroblasts is Associated With Atrial Fibrosis and Regulates Cell Behaviors of Cardiac Fibroblasts

Abstract

Background: Tumor endothelial marker 1 (TEM1 or CD248) is a transmembrane protein that expresses in mesenchymal lineage-derived cells only during embryogenesis. Re-upregulation of TEM1 in fibroblasts has been found in hepatic fibrosis, renal fibrosis and wound healing. Atrial fibrosis plays an important role in atrial fibrillation (AF) and stroke. We evaluated TEM1 expression in atrial fibrosis and its physiological significance. Methods and Results: All data were presented as mean ± standard error. In 10 patients (pts) with AF undergoing indicated cardiac surgery and Maze procedure, left atrial (LA) appendage was excised. Immunofluorescence staining showed TEM1 expressed in LA cardiac fibroblasts (CFs) in AF pts but not in normal LA tissue purchased from the US Biomax, Inc. Sirius Red staining showed more LA fibrosis in AF than normal LA tissue (7.51±0.40% vs. 3.80±0.51%, p<0.01). In AF pts, higher LA TEM1 expression detected by western blotting was associated with larger LA fibrosis. In 20 AF pts (15 men, mean age 57.5 ± 2.8 yrs) undergoing catheter ablation, LA blood samples were taken and soluble TEM1 (sTEM1) was measured by ELISA. Peak atrial longitudinal strain (PALS) measured by speckle tracking echocardiography before ablation was used as an atrial fibrosis marker. There was a significantly negative correlation of the sTEM1 levels in LA with PALS (ρ=-0.453, p<0.05) indicating increased sTEM1 was associated with atrial fibrosis. In vitro study showed recombinant TEM1 protein (rTEM1) increased proliferation of cultured CFs (saline vs rTEM1 10, 50 and 100 nM, BrdU absorbance: 0.55±0.02 vs. 0.62±0.04 vs. 0.73±0.04 vs. 0.74±0.04, p<0.05) and reduced starvation-induced apoptosis (cell death ELISA absorbance: 1.06±0.09 vs. 0.61±0.05 vs. 0.49±0.11 vs. 0.33±0.02, p<0.05). Transwell assay showed rTEM1 induced increased CFs migration. Conclusions: The study results indicate that TEM1 upregulation in CFs is associated with atrial fibrosis and TEM1 changes the cell behaviors of CFs. Further studies are undergoing to clarify if TEM1 knockdown could alleviate atrial fibrosis.