doi: 10.1161/hc3301.094742
(Circulation. 2001;104:864.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Coexpression of Endothelin-Converting Enzyme-1 and Endothelin-1 in Different Stages of Human Atherosclerosis
From the Department of Pathology, University of Freiburg, Freiburg, Germany (C.I., H.E.S.); the Third Department of Internal Medicine, Semmelweis University of Budapest, Budapest, Hungary (T.S.); and F. Hoffmann LaRoche AG, Basel, Switzerland (B.B., M.B., B.M.L.).
Correspondence to Christian Ihling, MD, Department of Pathology, University of Freiburg, Albertsraße 19, 79104 Freiburg, Germany. E-mail cihling{at}gmx.de
Background—— Endothelin-converting enzyme (ECE)-1 activates endothelin-1 (ET-1) and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis.
Methods and Results—— To evaluate ECE-1 immunoreactivity concerning big ET-1/ET-1, we performed qualitative and quantitative immunohistochemistry in normal internal mammary arteries (n=10), in coronary arteries with adaptive intimal fibrosis (n=10), in aortic fatty streaks (n=10), and in distinct regions of advanced carotid plaques (n=15). Furthermore, we determined ECE-1 activity in the control specimens and in the inflammatory intimal regions of carotid plaques. Double immunolabeling showed that ECE-1 was present in endothelial cells, vascular smooth muscle cells, and macrophages. All ET-1+ cells were simultaneously ECE-1+. Most importantly, there were significantly more ET-1+ cells in the intima and media when atherosclerosis was in an inflammatory stage than when it was in a noninflammatory stage. Moreover, ECE-1 activity was upregulated in the intima of carotid plaques, although immunohistochemically, there were no significant differences between the number of ECE+ cells in the different compartments of the arterial wall.
Conclusion—— Together with ET-1, ECE-1 is abundantly present in human arteries and at different stages of atherosclerotic plaque evolution. The upregulation of the ECE-1/ET-1 system is closely linked to the presence of chronic inflammation and is present in very early stages of plaque evolution. Therefore, enhanced production of active ET-1 may substantially contribute to cell growth and the regulation of vascular tone in advanced atherosclerotic lesions and in the very early stages of plaque evolution, when a plaque is still imperceptible clinically.
Key Words: endothelin • atherosclerosis • inflammation
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