Hirulog-like peptide reduces restenosis and expression of tissue factor and transforming growth factor-beta in carotid artery of atherosclerotic rabbits.

Abstract

Restenosis is responsible to approximately 30% of long-term failure following therapeutic vascular procedures. Thrombosis plays a key role in the development of restenosis. Thrombin-specific inhibitors have been considered as one type of candidates for the prevention of restenosis. Previous studies by our group demonstrated that a novel thrombin-specific inhibitor, hirulog-like peptide (HLP), reduced balloon catheter-induced neointima formation in rat carotid arteries. The present study examined the effect of HLP on angioplasty-induced restenosis in carotid arteries of atherosclerotic rabbits. New Zealand white rabbits were subject to air desiccation of the lumen of the right carotid arteries, then received high cholesterol/fat diet for 3 weeks. The rabbits were intravenously infused with HLP (1.6 mg/(kg/h)) or saline (n=7 per group) for 4 h started before angioplasty which dilated atherosclerotic lesions in right common carotid artery. Four weeks after the angioplasty, neointimal area, stenosis and neointima/media ratio in injured carotid arteries were reduced in atherosclerotic rabbits treated with HLP compared to saline controls by 62, 39 and 59% (P<0.05). The expression of tissue factor (TF) and transforming growth factor (TGF)-beta in the neointima of carotid arteries of rabbits treated with HLP was significantly weaker than saline controls (P<0.05 or <0.01). Activated partial thromboplastin time and bleeding time in HLP-treated rabbits were not significantly prolonged compared to controls. The results of the present study suggest that HLP may substantially reduce angioplasty-induced restenosis in atherosclerotic rabbits without increasing bleeding tendency. The inhibition on the expression of TF and TGF-beta in the neointima of the arterial wall may contribute to the preventive effect of HLP on restenosis in atherosclerotic rabbits.

• Authors: Xing Chen, Song Ren, Miranda G Ma, Sudharshan Dharmalingam, Lin Lu, Mengzhou Xue, John Ducas, Garry X Shen
• Journal: Atherosclerosis (Atherosclerosis) Vol. 169 Issue 1 Pg. 31-40 (Jul 2003) ISSN: 0021-9150 [Print] Ireland
• PMID: 12860248 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hirudins
• Peptide Fragments
• Recombinant Proteins
• Transforming Growth Factor beta
• hirulog-like peptide
• Collagen
• Thromboplastin
• bivalirudin

Topics

• Animals
• Arteriosclerosis (metabolism, pathology)
• Bleeding Time
• Carotid Artery, Common (metabolism, pathology)
• Carotid Stenosis (metabolism, pathology)
• Collagen (metabolism)
• Hirudins (analogs & derivatives, pharmacology)
• Humans
• Immunohistochemistry
• Male
• Partial Thromboplastin Time
• Peptide Fragments (pharmacology)
• Rabbits
• Rats
• Recombinant Proteins (pharmacology)
• Recurrence
• Thromboplastin (metabolism)
• Transforming Growth Factor beta (metabolism)
• Tunica Intima (metabolism, pathology)