Achim Lother1, Stella Bergemann2, Lisa Deng2, Martin Moser2, Christoph Bode2, Lutz Hein2. 1. From the Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine (A.L., S.B., L.D., L.H.), Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine (A.L., M.M., C.B.), and BIOSS Centre for Biological Signaling Studies (L.H.), University of Freiburg, Germany. achim.lother@universitaets-herzzentrum.de. 2. From the Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine (A.L., S.B., L.D., L.H.), Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine (A.L., M.M., C.B.), and BIOSS Centre for Biological Signaling Studies (L.H.), University of Freiburg, Germany.
Abstract
OBJECTIVE: Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. APPROACH AND RESULTS: We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the Meox2/Tcf15, Fabp4, and Cd36 signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis. CONCLUSIONS: The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation.
OBJECTIVE: Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. APPROACH AND RESULTS: We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the Meox2/Tcf15, Fabp4, and Cd36 signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis. CONCLUSIONS: The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation.
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