Endothelin-converting enzyme expression in the rat vascular injury model and human coronary atherosclerosis.
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.


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 alpha-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.
Minamino
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Kurihara
H
H
Takahashi
M
M
Shimada
K
K
Maemura
K
K
Oda
H
H
Ishikawa
T
T
Uchiyama
T
T
Tanzawa
K
K
Yazaki
Y
Y
D000368:Aged; D000800:Angioplasty, Balloon; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000378:metabolism*; D002339:Carotid Arteries / Q000201:enzymology*; D020212:Carotid Artery Injuries; D003324:Coronary Artery Disease / Q000201:enzymology*; D003331:Coronary Vessels / Q000201:enzymology; D004195:Disease Models, Animal; D000072396:Endothelin-Converting Enzymes; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000201:enzymology / Q000503:physiopathology
D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes