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(Circulation. 2000;102:1086.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Tissue Endothelin-Converting Enzyme Activity Correlates With Cardiovascular Risk Factors in Coronary Artery Disease

Frank Ruschitzka, MD; Ueli Moehrlen, MD; Thomas Quaschning, MD; Mario Lachat, MD; Georg Noll, MD; Sidney Shaw, PhD; Zhihong Yang, MD; Daniel Teupser, MD; Thomas Subkowski, PhD; Marko I. Turina, MD; Thomas F. Lüscher, MD

From Cardiology, University Hospital and Cardiovascular Research, Institute of Physiology, University of Zürich (F.R., T.Q., G.N., Z.Y., T.F.L.); Cardiovascular Surgery, University Hospital Zürich (U.M., M.L., M.I.T.); and Department of Clinical Research, Inselspital Bern (S.S.), Switzerland; and BASF AG, Main Laboratory, Ludwigshafen (T.S.), and Department of Clinical Chemistry, University Hospital Grosshadern, Munich (D.T.), Germany.

Correspondence to Thomas F. Lüscher, MD, FRCP, FACC, FESC, Professor and Head of Cardiology, University Hospital, CH-8091 Zürich, Switzerland. E-mail frankruschitzka{at}yahoo.com

Background—Endothelin-converting enzymes (ECEs) are the key enzymes in endothelin-1 (ET-1) generation. However, their pathophysiological role in patients with cardiovascular disease remains elusive.

Methods and Results—Vascular reactivity to big endothelin-1 (bigET-1; 10^-9 to 10^-7 mol/L) and ET-1 (10^-9 to 10^-7 mol/L) were examined in the internal mammary artery (IMA, n=33) and saphenous vein (SV, n=27) of patients with coronary artery disease with identified cardiovascular risk factors. Vascular ECE activity was determined by conversion of exogenously added bigET-1 to ET-1. Tissue contents of bigET-1 and ET-1 were measured by radioimmunoassay. In addition, the effects of LDL and oxidized LDL on ECE-1 protein levels were determined by Western blot analysis in human IMA endothelial cells. In the IMA, vascular ECE activity showed an inverse correlation with serum LDL levels (r=-0.76; P<0.01) and systolic and diastolic blood pressure and a positive correlation with fibrinogen (r=0.58; P<0.05). In the SV, fibrinogen was the only parameter to be correlated with vascular ECE activity. Vascular tissue content of bigET-1 was attenuated in the IMA of patients with hyperfibrinogenemia but increased in patients with elevated systolic blood pressure and increased serum LDL levels (P<0.05). Most interestingly, LDL and oxidized LDL downregulated ECE-1 protein levels in human IMA endothelial cells (P<0.05).

Conclusions—These data demonstrate, for the first time, that vascular ECE activity is (1) inversely correlated with serum LDL levels and blood pressure and (2) positively associated with fibrinogen in human vascular tissue. Hence, ECE-1 activity may modulate cardiovascular risk in patients with coronary artery disease.

Key Words: endothelin • enzymes • arteries • lipoproteins • fibrinogen • blood pressure

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