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Cardiac expression patterns of endothelin‐converting enzyme (ECE) suggest a role of endothelin signaling in conduction system development
Author(s) -
Sedmera David,
Harris Brett S.,
Grant Elizabeth,
Zhang Ning,
Jourdan Jane,
Kurkova Dana,
Gourdie Robert G.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a201
Subject(s) - purkinje fibers , medicine , bosentan , endocrinology , endothelin receptor , endothelin 1 , electrical conduction system of the heart , heart development , biology , myocyte , microbiology and biotechnology , chemistry , embryonic stem cell , receptor , electrophysiology , electrocardiography , biochemistry , gene
Conversion of big‐endothelin (ET) into biologically active ET is performed proteolytically by endothelin‐converting enzyme (ECE). ET has ability to induce differentiation of embryonic myocytes into a Purkinje fiber‐like phenotype in vitro and in vivo. We have generated an antibody against chick ECE to correlate its cardiac expression patterns reported previously at mRNA level. On Western blot, the antibody recognized a single band at ~70 kD molecular mass. Immunohistochemically the protein expression was more widespread compared to RNA, being present in the endothelium, as well as in mesenchymal cells and myocytes, and enriched in the ventricular trabeculae and nascent ventricular conduction system. At later fetal and postnatal stages, the expression was more restricted to the coronary endothelium and periarterial Purkinje fibers, partially overlapping with connexin40 expression. The myocardial expression was significantly decreased in experimental left ventricular hypoplasia, correlating with conduction deficiencies reported in this model previously. Inhibition of ET signaling by ET receptor antagonist bosentan resulted in delay of bundle branches maturation. Together, ECE expression patterns are consistent with the role of ET signaling in conduction system induction during avian cardiac development. Supported by NIH HL56728, HD 39946, RR 16434; MECR VZ 206100–3, and ASCR AVOZ50450515.