Interferon-gamma inhibits in situ expression of PDGF-beta mRNA by smooth muscle cells in injured rabbit arteries after transluminal balloon angioplasty.
OBJECTIVE
To elucidate the mechanism of interferon-gamma (IFN-gamma) to inhibit the restenosis after successful percutaneous transluminal angioplasty (PTA).


METHODS
A rabbit vascular restenotic model was constructed and the proliferation of intimal smooth muscle cells (SMCs) were observed by monitoring their expression of proliferating cell nuclear antigen (PCNA) and platelet-derived growth factor beta chain mRNA (PDGF-beta mRNA) at the indicated time points.


RESULTS
IFN-gamma could significantly inhibit the expression of PCNA by intimal SMCs one week after denudation, when counting 200 intimal cells for PCNA-positive reactions with an inhibitory rate of 88.50% (P < 0.001). IFN-gamma could downregulate in situ expression of PDGF-beta mRNA by these cells as we calculated the average number of PDGF-beta mRNA positive cells per square millimetre area at x 400 magnification with reduced rates of 86.85% in 1 week group (P < 0.001), of 93.66% in 2 week group (P < 0.001) and of 52.92% in 4 week group (0.02 < P < 0.05), respectively.


CONCLUSIONS
The local production of PDGF-beta by vascular intimal SMCs via an autocrine mechanism may be responsible for continuous proliferation of these cells and the formation of neointima after injury. This could be inhibited by IFN-gamma through downregulating the expression of PDGF-beta mRNA. These results provide an in vivo basis for IFN-gamma to be used clinically for the management of restenosis after percutaneous transluminal angioplasty.
Ji
J
J
Shenzhen Sunyixian Cardiovascular Hospital, Shenzhen 518001, China.
Si
L
L
Fang
W
W
Ling
W
W
D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D007371:Interferon-gamma