Hepatocyte growth factor fusion protein having collagen-binding activity (CBD-HGF) accelerates re-endothelialization and intimal hyperplasia in balloon-injured rat carotid artery.
OBJECTIVE
Hepatocyte growth factor (HGF) is known to stimulate endothelial cell proliferation. However, re-endothelialization is not enhanced when the native protein is administered to the injured artery, probably due to the short half-life of HGF at the site of injury. Therefore, the effects of an HGF fusion protein having collagen-binding activity (CBD-HGF) on re-endothelialization and neointimal formation was studied in the balloon-injured rat carotid artery.


METHODS
The left common carotid artery of male Sprague-Dawley rats was injured with an inflated balloon catheter, and then treated with CBD-HGF 10 microg/mL), HGF (10 micro g/mL) or saline (control) for 15 min. After 14 days, the rats were injected with Evans blue and sacrificed.


RESULTS
The re-endothelialized area was significantly greater in the CBD-HGF- treated rats than in the control or HGF -treated rats. Neointimal formation was significantly more pronounced in the CBD-HGF treated rats than in other rat groups. Both HGF and CBD-HGF stimulated proliferation of vascular smooth muscle cells as well as endothelial cells in vitro. Consistent with this, cultured smooth muscle cells were shown to express the HGF receptor (c-Met).


CONCLUSIONS
CBD-HGF accelerates re-endothelialization and neointimal formation in vivo. CBD fusion protein is a useful vehicle to deliver vascular growth factors to injured arteries.
Ohkawara
Nana
N
Geriatrics and Vascular Medicine, Tokyo Medical and Dental University Graduate School, Japan.
Ueda
Hiroki
H
Shinozaki
Shohei
S
Kitajima
Takashi
T
Ito
Yoshihiro
Y
Asaoka
Hiroshi
H
Kawakami
Akio
A
Kaneko
Eiji
E
Shimokado
Kentaro
K
D000818:Animals; D001011:Aorta / Q000166:cytology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D011993:Recombinant Fusion Proteins; D017228:Hepatocyte Growth Factor; D003094:Collagen