Expression of tumor endothelial marker 1 in cardiac fibroblast contributes to atrial fibrosis in atrial fibrillation

Atrial fibrosis is associated with atrial fibrillation (AF) and stroke. Tumor endothelial marker 1 (TEM1/CD248) is a transmembrane protein that appears in mesenchymal lineage-derived cells only during embryogenesis. Re-upregulation of TEM1 in fibroblasts plays an important role in organ fibrosis. We evaluated TEM1 expression in atrial fibrosis of AF patients and its physiological significance. Left atrial (LA) appendages were collected from 30 AF patients (mean age 64.0 years, 76.7% male) who underwent indicated cardiac surgery. Immunofluorescence staining showed TEM1 expression in the atrial cardiac fibroblasts in AF but not in normal atrial tissue. Western blot could detect TEM1 expression in the LA tissues of all 30 AF patients. There was a positive correlation between the levels of TEM1 expression in western blot with the severity of atrial fibrosis. In animal experiment, angiotensin II (Ang II) infusion induced TEM1 expression and atrial fibrosis in mice. Atrial fibrosis was less severe in TEM1-deficient transgenic mice after Ang II infusion. TEM1 activated cardiac fibroblast and increased its proliferation, survival and migration. Our study results indicate that TEM1 re-expression in cardiac fibroblasts in AF is associated with severity of atrial fibrosis. TEM1 changes the cell behaviors of cardiac fibroblasts and contributes to atrial fibrosis.