Cardiac expression patterns of endothelin-converting enzyme (ECE): implications for conduction system development.
The spatiotemporal distribution of the endothelin-converting enzyme (ECE) protein in the embryonic chick heart and the association of this polypeptide with the developing cardiac conduction system is described here for the first time. Further, we show how cardiac hemodynamic load directly affects ECE level and distribution. Endothelin (ET) is a cytokine involved in the inductive recruitment of Purkinje fibers. ET is produced by proteolytic cleavage of Big-ET by ECE. We generated an antibody against chick ECE recognizing a single band at approximately 70 kD to correlate the cardiac expression of this protein with that reported previously for its mRNA. ECE protein expression was more widespread compared to its mRNA, being present in endothelial cells, mesenchymal cells, and myocytes, and particularly enriched in the trabeculae and nascent ventricular conduction system. The myocardial expression was significantly modified under experimentally altered hemodynamic loading. In vivo, ET receptor blockade with bosentan delayed activation sequence maturation. These data support a role for ECE in avian cardiac conduction system differentiation and maturation.
Sedmera
David
D
Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Harris
Brett S
BS
Grant
Elizabeth
E
Zhang
Ning
N
Jourdan
Jane
J
Kurkova
Dana
D
Gourdie
Robert G
RG
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D000077300:Bosentan; D002642:Chick Embryo; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D006439:Hemodynamics; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D011690:Purkinje Fibers / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013449:Sulfonamides / Q000378:metabolism; D013997:Time Factors
D016232:Endothelins; D012333:RNA, Messenger; D013449:Sulfonamides; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D000077300:Bosentan