Selective upregulation of endothelin B receptor gene expression in severe pulmonary hypertension.
BACKGROUND
The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. Increased plasma ET-1 levels are observed in pulmonary arterial hypertension (PHT) and may contribute to the regulation of pulmonary vascular resistance, as well as to proliferative changes in the pulmonary vascular bed.


RESULTS
We prospectively assessed changes in plasma big ET-1 levels and changes in ET(A) and ET(B) receptor gene expression in 14 consecutive patients undergoing pulmonary thromboendarterectomy for thromboembolic PHT. Plasma big ET-1 levels were higher in patients with PHT (median, 2.2 pg/mL; 25th to 75th percentile, 1.5 to 3.0 pg/mL) compared with age-matched controls (median, 1.2 pg/mL; 25th to 75th percentile, 1.0 to 1.4 pg/mL; P=0.002). In addition to increased plasma big ET-1 levels, selective upregulation of ET(B) receptor mRNA transcripts and immunoreactive protein in the pulmonary artery was observed in the patients; however, ET(A) receptor gene expression was unaffected.


CONCLUSIONS
These data suggest that changes in the ET signaling system in PHT caused by thromboembolic disease are not limited to an increased production of ET-1: they also affect ET receptor gene expression.
Bauer
Michael
M
Department of Anesthesiology, University of the Saarland, Homburg, Germany. aimbau@uniklinik-saarland.de
Wilkens
Heinrike
H
Langer
Frank
F
Schneider
Sven O
SO
Lausberg
Henning
H
Schäfers
Hans-Joachim
HJ
D004691:Endarterectomy; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood*; D005260:Female; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011651:Pulmonary Artery / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000150:complications / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin