Localization of heparin-binding epidermal growth factor-like growth factor in human coronary arteries. Possible roles of HB-EGF in the formation of coronary atherosclerosis.
BACKGROUND
Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a newly identified member of the EGF family. Our previous in vitro studies showed that HB-EGF is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs), suggesting the role of HB-EGF in the pathogenesis of atherosclerosis. The purposes of the present study were to investigate the localization of HB-EGF in both normal and atherosclerotic human coronary arteries and to elucidate the possible roles of this growth factor in the formation of atherosclerotic lesions.


RESULTS
The immunohistochemical localization of HB-EGF, SMCs, macrophages, and EGF receptors (EGFRs) was examined in human coronary arteries obtained at autopsy. The medial SMCs of coronary arteries in neonates, infants, and children consistently synthesized HB-EGF protein. In normal adults, however, the relative number of HB-EGF-positive medial SMCs decreased gradually with age after about 30 years of age. In nonatherosclerotic coronary arteries with diffuse intimal thickening, SMCs of the intima, especially those located in the area of the medial side of the intima, were strongly positive for HB-EGF protein. In atherosclerotic plaques of coronary arteries with eccentric intimal thickening, both SMCs and macrophages in and around the core lesions, in addition to the intimal and medial SMCs located adjacent to the plaque, produced HB-EGF protein. A strong immunostaining of EGFRs was observed in these SMCs, suggesting a close association of HB-EGF and EGFR expression.


CONCLUSIONS
These data suggest that HB-EGF might play important roles in the migration of SMCs from the media to the intima, the proliferation of intimal SMCs, and the interaction between SMCs and macrophages in the process of coronary atherogenesis.
Nakata
A
A
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Miyagawa
J
J
Yamashita
S
S
Nishida
M
M
Tamura
R
R
Yamamori
K
K
Nakamura
T
T
Nozaki
S
S
Kameda-Takemura
K
K
Kawata
S
S
Taniguchi
N
N
Higashiyama
S
S
Matsuzawa
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000502:physiology; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D014018:Tissue Distribution
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor