Abstract P293: Chronic Pressure Overload Impacts Cardiac Endothelial Cell and Macrophage Gene Expression

Abstract

Introduction: The heart is composed of various different cell types that show distinct differences in gene expression. Inflammation is a key driver of adverse cardiac remodeling and endothelial cells and macrophages are crucially involved in that process. Thus, the aim of this study was to investigate cell type-specific changes in gene expression in cardiac endothelial cells and macrophages after left ventricular pressure overload. Methods and Results: Wildtype mice underwent transverse aortic constriction (TAC) to induce cardiac remodeling. After pressure overload, the number of macrophages in the heart increased about 3-fold (TAC 1755 ± 214 vs. CTRL 533 ± 76 macrophages / mg tissue, P < 0.001) as determined by flow cytometry. Lectin + endothelial cells and CD45 + CD11b + F4/80 high Ly6C low macrophages from CTRL and pressure overloaded hearts were isolated by fluorescence-assisted cell sorting. Cell type-specific gene expression was determined by RNAseq. We found 207 genes differentially expressed in cardiac endothelial cells isolated from pressure overloaded vs. CTRL hearts (n = 3-4 per group, q < 0.05). Approximately 25 % (52 genes) of these genes were highly enriched in endothelial cells vs. heart tissue (> 8-fold, q < 0.05). In cardiac macrophages, 1.359 genes were differentially expressed after pressure overload (n = 4-5 per group, q < 0.05). Bioinformatics analysis were performed to identify affected gene networks and putative key transcription factors involved in the regulation of these genes during cardiac remodeling. Integration of these datasets allowed to determine common, distinct and potentially interacting features of gene expression in both cell types. Conclusion: Chronic pressure overload induces distinct changes in gene expression in isolated cardiac endothelial cells and macrophages. Ongoing epigenetic analysis will provide insight into mechanisms of cell type-specific transcriptional regulation in these cells during cardiac remodeling.