Expression and activity of pulmonary endothelin converting enzyme in heart failure: Relation to endothelin biosynthesis and receptor distribution

Adviye Ergul, Ashley L. Grubbs, Yuhua Zhang, Cassandra Joffs, Jeffrey A. Sample, Mary K. King, Francis G. Spinale

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalJournal of Cardiac Failure
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2001

Fingerprint

Endothelin Receptors
Heart Failure
Endothelin-1
Lung
Proteins
Endothelin A Receptors
Endothelin-Converting Enzymes
Swine
Gene Expression
Messenger RNA

Keywords

  • Congestive heart failure
  • Endothelin converting enzyme
  • Endothelins
  • Experimental
  • Molecular biology
  • Pulmonary system
  • Receptor subtype

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Expression and activity of pulmonary endothelin converting enzyme in heart failure : Relation to endothelin biosynthesis and receptor distribution. / Ergul, Adviye; Grubbs, Ashley L.; Zhang, Yuhua; Joffs, Cassandra; Sample, Jeffrey A.; King, Mary K.; Spinale, Francis G.

In: Journal of Cardiac Failure, Vol. 7, No. 1, 01.01.2001, p. 84-91.

Research output: Contribution to journalArticle

Ergul, Adviye ; Grubbs, Ashley L. ; Zhang, Yuhua ; Joffs, Cassandra ; Sample, Jeffrey A. ; King, Mary K. ; Spinale, Francis G. / Expression and activity of pulmonary endothelin converting enzyme in heart failure : Relation to endothelin biosynthesis and receptor distribution. In: Journal of Cardiac Failure. 2001 ; Vol. 7, No. 1. pp. 84-91.
@article{8472d75c90d94fab8d0142a6a16e92e7,
title = "Expression and activity of pulmonary endothelin converting enzyme in heart failure: Relation to endothelin biosynthesis and receptor distribution",
abstract = "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.",
keywords = "Congestive heart failure, Endothelin converting enzyme, Endothelins, Experimental, Molecular biology, Pulmonary system, Receptor subtype",
author = "Adviye Ergul and Grubbs, {Ashley L.} and Yuhua Zhang and Cassandra Joffs and Sample, {Jeffrey A.} and King, {Mary K.} and Spinale, {Francis G.}",
year = "2001",
month = "1",
day = "1",
doi = "10.1054/jcaf.2001.22423",
language = "English (US)",
volume = "7",
pages = "84--91",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "1",

}

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 - 2001/1/1

Y1 - 2001/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=0035068104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035068104&partnerID=8YFLogxK

U2 - 10.1054/jcaf.2001.22423

DO - 10.1054/jcaf.2001.22423

M3 - Article

C2 - 11264554

AN - SCOPUS:0035068104

VL - 7

SP - 84

EP - 91

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 1

ER -