Abstract 2166: Contribution of Epicardium-derived Cells to Annulus Fibrosis: Proof by Genetic Fate Map
Abnormal existence of accessory pathway provides anatomical substrates of Wolff-Parkinson-White syndrome, an arryhthmia in humans. Recent studies showed that th development of annulus fibrosis is related to persistent of accessory pathways. Understanding the cellular contribution in the annulus fibrosis (AF) is important for the aetiology of accessory atriventricular pathway-mediated reentrant tachycardia (AVRT). Here we used Cre-LoxP technology to specifically trace epicardium derived cells (EPDCs) and detected their contribution in annulus fibrosis at later stages during cardiogenesis. We found a subset of EPDCs migrated into the border between atrioventricular and separated their myocardium connection between atria and ventricles. In addition, we found these EPDCs expressed periostin and procollagen I, markers for fibroblast in annulus fibrosis. To distinguish whether the EPDCs secret periostin themselves or EPDCs only migrate to periostin-enriched AF region, we dissociated AF EPDCs by lineage trace reporter GFP and measured the gene expression by quantitative PCR. These EPDCs are higly enriched in periostin, fibronectin, procollagen I, vimentin, while EPDCs exhibit highly upregulated markers for epithelial to mesenchymal transition like Snail, Smad, Slug, Twist. Our work provided for the first time the definitive evidence that EPDCs contribute to the formation of annulus fibrosis, indicating its cellular basis for pathophysiology of accessory atriventricular pathway-mediated reentrant tachycardia.
This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).