Fibroblast-Endothelial Cell Interactions in the Heart
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Angiogenesis in the heart requires cell-cell communication between fibroblasts and endothelial cells (ECs). We have demonstrated that fibroblast-EC interactions involve the cell surface molecule N-cadherin. In tube formation assays, co-culturing ECs with fibroblasts and N-cadherin blocking antibodies decreased tube formation. Moreover, our studies demonstrated that cell-cell interactions between fibroblasts and ECs result in altered gene and protein expression, specifically with the pro-angiogenic factors IL-6, MCP-1 and VEGF. These changes in expression for IL-6 and MCP-1 require direct cell-cell interactions, while VEGF regulation is through indirect interactions. We have previously shown that fibroblasts and ECs can exchange intracellular material through tight gap junctions both in vitro and in vivo. We hypothesize that small microRNAs (miRNAs) can pass freely through these tight gap junctions. Our initial studies have focused on the pro-angiogenic miRNA, let-7f, which we have shown passes between fibroblasts and ECs and aids in vascular remodeling in the heart. We will continue to characterize the exchange of intracellular materials between cells and examine their roles in the vascular remodeling process following cardiac injury.