Abstract 14667: Endothelial-specific Loss of Primary Cilia Exacerbates Cardiac Fibrosis

Introduction: Cardiac fibrosis after injury, which significantly compromises heart function, is in part due to proliferation of fibroblasts of unclear cellular origin. Primary cilia are cellular protrusions that serve as mechanosensors for fluid flow. Loss of endothelial cilia coincides with endothelial-mesenchymal transition (EndMT), however the driving mechanism linking endothelial cilia and cardiac fibrosis remain mainly unexplored Methods: To elucidate the involvement of endothelial cilia in cardiac fibrosis in vivo and in vitro, we generated endothelial cell-specific Ift88-knockout mice (Ift88endo) and silenced Ift88 in human coronary artery endothelial cells (HCAECs), respectively to evaluate EndMT and fibrosis. Results: Silencing of Ift88 in HCAECs resulted in loss of endothelial cilia. A microscopic evaluation revealed mesenchymal cells-like morphological and ultra-structural changes in Ift88-silenced cells. Expression of endothelial markers, CD31, Tie-2 and VE-cadherin, were significantly low wit...