Selective upregulation of endothelin converting enzyme-1a in the human failing heart

Adviye Ergul, A. L. Grubbs, Y. Zhang, F. G. Spinale

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Increased plasma levels of endothelin-1 (ET-1) occur with congestive heart failure (CHF), but the components of the enzymatic activation of ET-1 in the myocardium remain to be defined. Accordingly, endothelin converting enzyme-1 (ECE-1) activity and expression in normal and failing heart were examined. Methods and Results: Left ventricular (LV) tissue samples were obtained from patients undergoing heart transplantation because of dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) and from normal donor hearts. The gene expression of ET-1 precursor and ECE-1a was upregulated 4- and 3-fold, respectively, in the failing heart. ECE-1 activity (fmol/mg protein per hour) was augmented from 2,291 ± 257 in normal tissue samples to 5,507 ± 666 in DCM samples and to 7,435 ± 682 in ICM samples (P < .05). Phosphoramidon and a specific ECE-1 inhibitor, FR901533, inhibited ECE-1 activity by over 90%. However, inhibitors of neutral endopeptidase (thiorphan) and matrix metalloproteases (batimistat) did not affect the conversion of big ET-1 to ET-1. Conclusions: This study showed that the biosynthetic pathway of ET-1 is activated in LV myocardium in the failing heart, and the myocardial processing of big ET-1 is highly specific for ECE-1.

Original languageEnglish (US)
Pages (from-to)314-320
Number of pages7
JournalJournal of Cardiac Failure
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2000

Fingerprint

Endothelin-1
Up-Regulation
Dilated Cardiomyopathy
Cardiomyopathies
Myocardium
Thiorphan
Neprilysin
Biosynthetic Pathways
Metalloproteases
Enzyme Inhibitors
Heart Transplantation
Endothelin-Converting Enzymes
Heart Failure
Tissue Donors
Gene Expression
Proteins

Keywords

  • Cardiomyopathy
  • Congestive heart failure
  • Myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Selective upregulation of endothelin converting enzyme-1a in the human failing heart. / Ergul, Adviye; Grubbs, A. L.; Zhang, Y.; Spinale, F. G.

In: Journal of Cardiac Failure, Vol. 6, No. 4, 01.01.2000, p. 314-320.

Research output: Contribution to journalArticle

Ergul, Adviye ; Grubbs, A. L. ; Zhang, Y. ; Spinale, F. G. / Selective upregulation of endothelin converting enzyme-1a in the human failing heart. In: Journal of Cardiac Failure. 2000 ; Vol. 6, No. 4. pp. 314-320.
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