Effect of hirulog-like peptide on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs and relationship with inflammatory mediators.
Vascular intervention-induced neointimal formation is a major drawback for managing atherosclerotic cardiovascular diseases using invasive vascular procedures. Our previous studies demonstrated that hirulog-like peptide (HLP) reduced balloon catheter dilation-induced neointimal formation or restenosis in carotid arteries of rats or atherosclerotic rabbits with less interruption in coagulation or bleeding than heparin or hirulog-1. The present study examined the effect of HLP on balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. Intravenous infusion of HLP (1.6 mg/kg/h for 4 h started 0.5 h before the intervention) or unfractured heparin (50 U/kg/h for 4 h) significantly reduced neointimal formation in femoral arteries 4 weeks after intervention compared with the vehicle. Heparin, but not HLP, significantly prolonged activated partial thromboplastin time. HLP or heparin significantly reduced vascular intervention-induced increases in C-reactive protein, P-selectin and interleukin-6 in serum. HLP, but not heparin, normalized vascular injury-induced increase in P-selectin in platelets. The results of the present study suggest that HLP is an effective agent for preventing balloon catheter injury-induced neointimal formation in femoral arteries of minipigs. The beneficial effects of HLP on vascular injury-induced neointimal formation may partially result from its inhibition on inflammatory mediators.
Tang
Xiao-Feng
XF
Shanghai Key Laboratory of Vascular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Liu
Jian-Jun
JJ
Wu
Yong-Jie
YJ
Chen
Ke-Ming
KM
Jin
Yong
Y
Gao
Ping-Jin
PJ
Zhu
Ding-Liang
DL
Shen
Garry X
GX
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D002404:Catheterization / Q000009:adverse effects*; D005263:Femoral Artery / Q000187:drug effects* / Q000276:immunology / Q000293:injuries / Q000473:pathology; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006629:Hirudins / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood*; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D023421:Models, Animal; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects* / Q000276:immunology / Q000293:injuries / Q000473:pathology
D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D006629:Hirudins; D018836:Inflammation Mediators; D015850:Interleukin-6; D019007:P-Selectin; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006493:Heparin; D002097:C-Reactive Protein; C074619:bivalirudin