title: Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis.
abstract: Endothelin-1 is a potent vasoconstrictor and exhibits a mitogenic activity on vascular smooth muscle cells (SMCs). Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin-1 processing. We studied the immunolocalization of ECE in human coronary atherosclerotic lesions with different disease stages. Frozen sections of normal coronary arteries with diffuse intimal thickening (n=13) and those of coronary arteries with early (n=10) or advanced atherosclerotic plaques (n=13) were studied. Monoclonal antibodies used were directed against SMCs, macrophages, endothelial cells, and ECE. For the identification of cell types that express ECE, double immunostaining analysis was also used. In normal coronary arteries, ECE immunoreactivity was observed in luminal endothelial cells and medial SMCs. Early atherosclerotic plaques, which consisted predominantly of SMCs, showed enhanced ECE expression in luminal endothelial cells and intimal SMCs. In advanced atherosclerotic plaques, distinct ECE expression was found in accumulated macrophages and in endothelial cells of intraplaque microvessels, while luminal endothelial cells showed relatively weak immunoreactivity for ECE. In conclusion, the present study demonstrates that the major cell types expressing ECE within the plaques are different between early and advanced stages of human coronary atherosclerosis. Enhanced ECE expression and possible endothelin-1 generation may contribute to SMC proliferation and vasoconstriction in early atherosclerotic stages, and may promote plaque destabilization in advanced atherosclerotic stages.
authors.affiliation: Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Eishu
authors.initials: E
authors.lastname: Hai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shirai
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshimi
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kayo
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Sugama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fujino
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ohsawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tanzawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokota
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D003331:Coronary Vessels / Q000201:enzymology / Q000473:pathology; D000072396:Endothelin-Converting Enzymes; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D008666:Metalloendopeptidases; D008875:Middle Aged
chemical_list: D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes