Expression of endothelin-converting enzyme, endothelin-1 and endothelin receptors at the site of percutaneous coronary intervention in humans.
OBJECTIVE
The repair process at the site of injury after percutaneous coronary intervention (PCI) is dominated by neointimal formation composed mainly of smooth muscle cells (SMC). Endothelin-1 (ET-1) is a powerful vasoconstrictor and SMC mitogen. Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin processing. The effects of ET-1 are mediated by binding to endothelin type A (ETA) and endothelin type B (ETB) receptors. The ligand/receptor/ligand-producing system (ET system) could be involved in the pathogenesis of neointimal formation in humans.


METHODS
Fifteen post-PCI sites obtained at autopsy and eight atherectomy specimens obtained from restenotic sites were investigated using immunohistochemical single and double staining techniques. Frozen sections were stained with antibodies against ECE, ET-1, ETA and ETB receptors, SMC, macrophages and endothelial cells.


RESULTS
At the early stage, less than 3 months after PCI, neointimal SMC were positive for ECE, ET-1, ETA and ETB receptors. The expression of ECE, ET-1, ETA and ETB receptors in these neointimal SMC decreased markedly from 6 months onwards. The ECE, ET-1, ETA and ETB receptor-positive cell areas were significantly (P < 0.005) greater in the first 3 months after PCI compared with 6 months or more after PCI. Atherectomy specimens also showed similar positivity.


CONCLUSIONS
These observations strongly suggest that the expression of ECE, ET-1, ETA and ETB receptors is enhanced in neointimal SMC at early stages after PCI injury in human coronary arteries. The increased expression of the ET system may contribute to SMC proliferation/migration and vasoconstriction in human post-PCI coronary lesions.
Department of Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Nobuyuki
N
Shirai
Takahiko
T
Naruko
Masahiko
M
Ohsawa
Yoshihiro
Y
Ikura
Yoshimi
Y
Sugama
Michihiko
M
Hirayama
Chizuko
C
Kitabayashi
Shoichi
S
Ehara
Takeshi
T
Inoue
Akira
A
Itoh
Kazuo
K
Haze
Kazuhiko
K
Tanzawa
Minoru
M
Yoshiyama
Junichi
J
Yoshikawa
Makiko
M
Ueda
D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D017225:Atherectomy, Coronary; D001344:Autopsy; D003331:Coronary Vessels / Q000378:metabolism* / Q000601:surgery; D019332:Endothelin-1 / Q000096:biosynthesis*; D000072396:Endothelin-Converting Enzymes; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000096:biosynthesis; D044023:Receptor, Endothelin B / Q000096:biosynthesis; D017466:Receptors, Endothelin / Q000096:biosynthesis*; D017539:Tunica Intima / Q000378:metabolism
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes