Halofuginone, a specific collagen type I inhibitor, reduces anastomotic intimal hyperplasia.
OBJECTIVE
To determine if halofuginone hydrobromide, a specific type I collagen inhibitor, could prevent intimal hyperplasia at a vascular anastomosis.


METHODS
Intimal hyperplasia is characterized by smooth muscle cell proliferation and extracellular matrix accumulation. Halofuginone was used to block collagen production and smooth muscle cell proliferation in cell cultures and in a rabbit model of an end-to-end anastomosis of the right common carotid artery. Animals were fed a nontoxic dose of halofuginone. Eighteen rabbits were fed the inhibitor in a randomized blinded fashion and were examined after 4 weeks by harvesting the arteries after perfusion fixation at physiologic pressures.


RESULTS
Halofuginone inhibited smooth muscle cell proliferation in vitro and had no effect on cell viability. Morphometric quantification verified that halofuginone treatment significantly attenuated anastomotic intimal thickness.


CONCLUSIONS
Oral administration of halofuginone inhibits intimal hyperplasia at vascular anastomoses. Intimal hyperplasia inhibition by halofuginone may be a therapeutic option for preventing arterial stenosis in vascular surgery.
Choi
E T
ET
Department of Surgery, Washington University School of Medicine, St. Louis, Mo.
Callow
A D
AD
Sehgal
N L
NL
Brown
D M
DM
Ryan
U S
US
D000714:Anastomosis, Surgical / Q000009:adverse effects*; D000818:Animals; D015152:Blotting, Northern; D017536:Carotid Artery, Common / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery; D010880:Piperidines; D011347:Procollagen / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D011799:Quinazolines / Q000008:administration & dosage / Q000494:pharmacology*; D052999:Quinazolinones; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011817:Rabbits; D014333:Tropoelastin / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology* / Q000601:surgery
D010880:Piperidines; D011347:Procollagen; D011799:Quinazolines; D052999:Quinazolinones; D012333:RNA, Messenger; D014333:Tropoelastin; D003094:Collagen; C010176:halofuginone