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(Circulation. 1997;95:221-230.)
© 1997 American Heart Association, Inc.
Articles |
Endothelin-Converting Enzyme Expression in the Rat Vascular Injury Model and Human Coronary Atherosclerosis
the Third Department of Internal Medicine (T.M., H.K., K.M., Y.Y.), Department of Pathology (H.O., T.I.), Faculty of Medicine, University of Tokyo; The Biological Research Laboratories, Sankyo Co Ltd (M.T., K.S., K.T.), Tokyo; and Hachioji Medical Center of Tokyo Medical College (T.U.), Japan.
Correspondence to Hiroki Kurihara, MD, PhD, The Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. E-mail kuri-tky@umin.u-tokyo.ac.jp.
Background Endothelin 1 has been implicated in various human diseases, including atherosclerosis. In this study, we examined the expression and localization of endothelin-converting enzyme-1 (ECE-1), the final key enzyme of endothelin 1 processing, in rat carotid arteries after balloon injury and in human coronary atherosclerotic lesions.
Methods and Results ECE-1 mRNA levels and ECE activity in rat balloon-injured arteries started to increase between 2 and 5 days after injury. The endothelin 1 content of tissue in injured arteries was concomitantly increased. Immunohistochemical staining located ECE-1 signals in endothelial cells in uninjured arteries, whereas ECE-1 immunoreactivity was detected in neointimal smooth muscle cells in injured arteries 5 to 14 days after balloon denudation. The size of the neointima was effectively reduced by phosphoramidon, an inhibitor of neutral metalloproteases, including ECE-1. In human coronary atherosclerotic lesions, intense ECE-1 immunoreactivity was detected in subsets of cells embedded in atheromatous plaque that correspond to smooth muscle cells and macrophages, as identified by staining for smooth muscle 
-actin and CD68 surface marker, respectively.
Conclusions The present study ascertained that ECE-1 is expressed in neointimal smooth muscle cells in rat balloon-injured arteries and in both smooth muscle cells and macrophages in human coronary atherosclerotic lesions. Blockade of ECE-1 was effective in reducing neointimal formation after balloon injury. Thus, ECE-1 may contribute to the process of injury-induced neointimal formation and atherosclerosis through the autocrine/paracrine effects of endothelin 1.
Key Words: atherosclerosis • endothelin • enzymes
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