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פותח על ידי קלירמאש פתרונות בע"מ -
Inhibition of collagen synthesis, smooth muscle cell proliferation, and injury-induced intimal hyperplasia by halofuginone
Year:
1997
Authors :
גנין, אולגה
;
.
פינס, מרק
;
.
Volume :
17
Co-Authors:
Nagler, A., Depts. of Bone Marrow Transplant., Hadassah-Hebrew University Hospital, Jerusalem, Israel
Miao, H.-Q., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel
Aingorn, H., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Genina, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Vlodavsky, I., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel, Department of Oncology, Hadassah Hospital, PO Box 12 000, Jerusalem 91120, Israel
Facilitators :
From page:
194
To page:
202
(
Total pages:
9
)
Abstract:
Proliferation of vascular smooth muscle cells (SMCs) and accumulation of extracellular matrix (ECM) components within the arterial wall in response to local injury are important etiologic factors in vascular proliferative disorders such as arteriosclerosis and restenosis after angioplasty. Fibrillar and nonfibrillar collagens are major constituents of the ECM that modulate cell shape and proliferative responses and thereby contribute to the pathogenesis of intimal hyperplasia. Halofuginone, an anticoccidial quinoazolinone derivative, inhibits collagen type I gene expression. We investigated the effect of halofuginone on (1) proliferation of bovine aortic endothelial cells and SMCs derived from the same specimen and maintained in vitro, (2) ECM deposition and collagen type I synthesis and gene expression, and (3) injury-induced intimal hyperplasia in vivo. DNA synthesis and proliferation of vascular SMCs in response to serum or basic fibroblast growth factor were abrogated in the presence of as little as 0.1 μg/mL halofuginone; this inhibition was reversible upon removal of the compound. Under the same conditions, halofuginone exerted a relatively small antiproliferative effect on the respective vascular endothelial cells. Halofuginone also inhibited the synthesis and deposition of ECM components by vascular SMCs as indicated both by a substantial reduction in the amount of sulfated proteoglycans and collagen type I synthesis and gene expression. Local administration of halofuginone in the rabbit ear model of crush injury- induced arterial intimal hyperplasia resulted in a 50% reduction in intimal thickening as measured by a morphometric analysis of the neointima/media ratio. The differential inhibitory effect of halofuginone on vascular SMCs versus endothelial cells, its inhibition of ECM deposition and collagen type I synthesis, and its ability to attenuate injury-induced intimal hyperplasia may place halofuginone alone or in combination with other antiproliferative compounds as a potential candidate for prevention of arterial stenosis and accelerated atherosclerosis.
Note:
Related Files :
animal cell
Animals
artery intima proliferation
cattle
Cell Division
Cell Proliferation
endothelium cell
Rabbits
restenosis
עוד תגיות
תוכן קשור
More details
DOI :
Article number:
Affiliations:
Database:
סקופוס
Publication Type:
מאמר
;
.
Language:
אנגלית
Editors' remarks:
ID:
31458
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 01:02
Scientific Publication
Inhibition of collagen synthesis, smooth muscle cell proliferation, and injury-induced intimal hyperplasia by halofuginone
17
Nagler, A., Depts. of Bone Marrow Transplant., Hadassah-Hebrew University Hospital, Jerusalem, Israel
Miao, H.-Q., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel
Aingorn, H., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Genina, O., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel
Vlodavsky, I., Department of Oncology, Hadassah-Hebrew University Hospital, Jerusalem, Israel, Department of Oncology, Hadassah Hospital, PO Box 12 000, Jerusalem 91120, Israel
Inhibition of collagen synthesis, smooth muscle cell proliferation, and injury-induced intimal hyperplasia by halofuginone
Proliferation of vascular smooth muscle cells (SMCs) and accumulation of extracellular matrix (ECM) components within the arterial wall in response to local injury are important etiologic factors in vascular proliferative disorders such as arteriosclerosis and restenosis after angioplasty. Fibrillar and nonfibrillar collagens are major constituents of the ECM that modulate cell shape and proliferative responses and thereby contribute to the pathogenesis of intimal hyperplasia. Halofuginone, an anticoccidial quinoazolinone derivative, inhibits collagen type I gene expression. We investigated the effect of halofuginone on (1) proliferation of bovine aortic endothelial cells and SMCs derived from the same specimen and maintained in vitro, (2) ECM deposition and collagen type I synthesis and gene expression, and (3) injury-induced intimal hyperplasia in vivo. DNA synthesis and proliferation of vascular SMCs in response to serum or basic fibroblast growth factor were abrogated in the presence of as little as 0.1 μg/mL halofuginone; this inhibition was reversible upon removal of the compound. Under the same conditions, halofuginone exerted a relatively small antiproliferative effect on the respective vascular endothelial cells. Halofuginone also inhibited the synthesis and deposition of ECM components by vascular SMCs as indicated both by a substantial reduction in the amount of sulfated proteoglycans and collagen type I synthesis and gene expression. Local administration of halofuginone in the rabbit ear model of crush injury- induced arterial intimal hyperplasia resulted in a 50% reduction in intimal thickening as measured by a morphometric analysis of the neointima/media ratio. The differential inhibitory effect of halofuginone on vascular SMCs versus endothelial cells, its inhibition of ECM deposition and collagen type I synthesis, and its ability to attenuate injury-induced intimal hyperplasia may place halofuginone alone or in combination with other antiproliferative compounds as a potential candidate for prevention of arterial stenosis and accelerated atherosclerosis.
Scientific Publication
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