J Vasc Res 2010;47:262-269

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Xiao-Feng Tang^{a, c}, Jian-Jun Liu^{a, c}, Yong-Jie Wu^{a, c}, Ke-Ming Chen^b, Yong Jin^b, Ping-Jin Gao^{a, c}, Ding-Liang Zhu^{a, c}, Garry X. Shen<sup>d

a</sup>Shanghai Key Laboratory of Vascular Biology,
^bDepartment of Radiology, and
^cRuijin Hospital, Shanghai Institute of Hypertension, Shanghai Jiaotong University School of Medicine, Shanghai, China;
^dDepartments of Internal Medicine and Physiology, University of Manitoba, Winnipeg, Man., Canada

Abstract

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.