TY - JOUR
T1 - Expression and activity of pulmonary endothelin converting enzyme in heart failure
T2 - Relation to endothelin biosynthesis and receptor distribution
AU - Ergul, Adviye
AU - Grubbs, Ashley L.
AU - Zhang, Yuhua
AU - Joffs, Cassandra
AU - Sample, Jeffrey A.
AU - King, Mary K.
AU - Spinale, Francis G.
PY - 2001
Y1 - 2001
N2 - Background: Although reduced pulmonary clearance of endothelin-1 (ET-1) has been suggested to contribute to increased circulating levels in congestive heart failure (CHF), the regulation of the pulmonary ET system with CHF remains to be defined. Accordingly, the aim of the present study is to investigate the expression and activity of the ET system with the development of CHF. Methods and Results: Pulmonary tissue samples were collected from pigs with pacing CHF (240 bpm, 3 wks, n = 10) and controls (n = 10). The pulmonary messenger RNA (mRNA) and protein levels of endothelin converting enzyme-1 (ECE-1) subisoforms, ET-1, and ET receptor profiles were determined. The gene expression of ET-1 precursor, ECE-1a, and ETA was upregulated 4-, 3-, and 2-fold, respectively, with CHF. Pulmonary tissue ET-1 was increased to 13 + 2 fmol/mg protein from control values of 5 ± 1 fmol/mg protein (P < .05), and ECE-1 activity was augmented from 3,264 ± 665 fmol/mg protein in control animals to 14,073 ± 654 fmol/mg protein per hour in CHF animals (P < .05). The ETB receptor density decreased, whereas ETA receptors were increased in CHF, indicating a shift in the ETA to ETB ratio. Conclusions: Both the increased synthesis and the decreased clearance of ET-1 via ETB receptors may contribute to the increased systemic and pulmonary ET-1 levels in CHF.
AB - Background: Although reduced pulmonary clearance of endothelin-1 (ET-1) has been suggested to contribute to increased circulating levels in congestive heart failure (CHF), the regulation of the pulmonary ET system with CHF remains to be defined. Accordingly, the aim of the present study is to investigate the expression and activity of the ET system with the development of CHF. Methods and Results: Pulmonary tissue samples were collected from pigs with pacing CHF (240 bpm, 3 wks, n = 10) and controls (n = 10). The pulmonary messenger RNA (mRNA) and protein levels of endothelin converting enzyme-1 (ECE-1) subisoforms, ET-1, and ET receptor profiles were determined. The gene expression of ET-1 precursor, ECE-1a, and ETA was upregulated 4-, 3-, and 2-fold, respectively, with CHF. Pulmonary tissue ET-1 was increased to 13 + 2 fmol/mg protein from control values of 5 ± 1 fmol/mg protein (P < .05), and ECE-1 activity was augmented from 3,264 ± 665 fmol/mg protein in control animals to 14,073 ± 654 fmol/mg protein per hour in CHF animals (P < .05). The ETB receptor density decreased, whereas ETA receptors were increased in CHF, indicating a shift in the ETA to ETB ratio. Conclusions: Both the increased synthesis and the decreased clearance of ET-1 via ETB receptors may contribute to the increased systemic and pulmonary ET-1 levels in CHF.
KW - Congestive heart failure
KW - Endothelin converting enzyme
KW - Endothelins
KW - Experimental
KW - Molecular biology
KW - Pulmonary system
KW - Receptor subtype
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U2 - 10.1054/jcaf.2001.22423
DO - 10.1054/jcaf.2001.22423
M3 - Article
C2 - 11264554
AN - SCOPUS:0035068104
SN - 1071-9164
VL - 7
SP - 84
EP - 91
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 1
ER -