Epicardial mesothelial cells synthesize and release endothelin.
Adult rat ventricular cardiocytes, when cocultured with epicardial mesothelial cells (EMC), demonstrate remarkable plasticity of phenotype accompanied by a significant increase in cardiocyte contractile protein content, suggesting that a factor with growth-promoting properties may take part in EMC-adult rat ventricular cardiocyte interactions. Endothelin (ET) has been shown to induce cell hypertrophy, including enhancement of expression of muscle-specific genes. We investigated the ability of EMC to synthesize and release ET. By light microscopy, specific immunostaining, with either ET-1 or Big ET-1 antibodies, was visualized in EMC as a fine punctate distributed throughout the cytoplasm. Reverse phase-high performance liquid chromatography (HPLC) of epicardial mesothelial cells conditioned medium showed several peaks of immunoreactive ET. The major peak eluted with the same retention time as that of ET-1. By Northern blot analysis, a specific 2.3-kilobase (kb) mRNA species was detected by hybridization to a cDNA insert encoding for rat prepro-ET-1. ET accumulated in the culture medium in a time-dependent manner, whereas cell content remained comparatively low. Angiotensin II (AII) dose-dependently stimulated release of immunoreactive ET into the culture medium.
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University of Ottawa Heart Institute, Ontario, Canada.
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Chen
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D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics / Q000633:toxicity; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D008854:Microscopy, Electron; D009693:Nucleic Acid Hybridization; D010496:Pericardium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D016232:Endothelins; D012333:RNA, Messenger; D000804:Angiotensin II