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      Hirulog-Like Peptide Reduces Balloon Catheter Injury Induced Neointima Formation in Rat Carotid Artery without Increase in Bleeding Tendency


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          Abstract: Vascular restenosis is one of the major concerns for the management of coronary artery disease using therapeutic vascular procedures. Treatments with thrombin-specific inhibitors, hirudin or hirulog-1, reduced ischemic events in coronary artery disease patients. Early started and prolonged infusions of these thrombin inhibitors partially prevented balloon catheter injury induced restenosis or neointima formation in experimental animal models, but increased the bleeding tendency. Hirulog-like peptide (HLP) was rationally designed to enhance the inhibition of the binding of thrombin to its receptor with less interruption of coagulation activity in comparison to hirulog-1. A single infusion of HLP for 4 h started 0.5 h before balloon catheter injury reduced neointima formation by 36% in rat carotid artery compared to vehicle controls. Tail bleeding time and activated partial thromboplastin time during HLP infusion were not significantly different from vehicle controls, but were significantly shorter than during heparin or hirulog-1 infusion. HLP treatment attenuated the expression of platelet-derived growth factor in the neointima of injured arteries. HLP also inhibited thrombin-induced thymidine incorporation in cultured baboon aortic smooth muscle cells. The findings suggest that HLP may substantially inhibit balloon catheter injury induced neointima formation without noticeable increase in bleeding tendency in rats. The inhibition by HLP of the expression of platelet-derived growth factor and of the smooth muscle cell proliferation in the vascular wall potentially contributes to the preventive effect of the new thrombin inhibitor on injury-induced neointima formation in the vascular wall.

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          Most cited references 6

          • Record: found
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          Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation.

          We isolated a cDNA encoding a functional human thrombin receptor by direct expression cloning in Xenopus oocytes. mRNA encoding this receptor was detected in human platelets and vascular endothelial cells. The deduced amino acid sequence revealed a new member of the seven transmembrane domain receptor family with a large amino-terminal extracellular extension containing a remarkable feature. A putative thrombin cleavage site (LDPR/S) resembling the activation cleavage site in the zymogen protein C (LDPR/I) was noted 41 amino acids carboxyl to the receptor's start methionine. A peptide mimicking the new amino terminus created by cleavage at R41 was a potent agonist for both thrombin receptor activation and platelet activation. "Uncleavable" mutant thrombin receptors failed to respond to thrombin but were responsive to the new amino-terminal peptide. These data reveal a novel signaling mechanism in which thrombin cleaves its receptor's amino-terminal extension to create a new receptor amino terminus that functions as a tethered ligand and activates the receptor.
            • Record: found
            • Abstract: not found
            • Article: not found

            The biology of platelet-derived growth factor.

              • Record: found
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              Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators.

              Heparin is often administered during and after coronary angioplasty to prevent closure of the dilated vessel. However, ischemic or hemorrhagic complications occur in 5 to 10 percent of treated patients. We studied whether these complications could be prevented when the direct thrombin inhibitor bivalirudin (Hirulog) was used in place of heparin. We performed a double-blind, randomized trial in 4098 patients undergoing angioplasty for unstable or postinfarction angina. Patients were assigned to receive either heparin or bivalirudin immediately before angioplasty. The primary end point were death in the hospital, myocardial infarction, abrupt vessel closure, or rapid clinical deterioration of cardiac origin. In the total study group, bivalirudin did not significantly reduce the incidence of the primary end point (11.4 percent, vs. 12.2 percent for heparin) but did result in a lower incidence of bleeding (3.8 percent vs. 9.8 percent, P < 0.001). In the prospectively stratified subgroup of 704 patients with postinfarction angina, bivalirudin therapy resulted in a lower incidence of the primary end point (9.1 percent vs. 14.2 percent, P = 0.04) and a lower incidence of bleeding (3.0 percent vs. 11.1 percent, P < 0.001), but in a similar cumulative rate of death, myocardial infarction, and repeated revascularization in the six months after angioplasty (20.5 percent vs. 25.1 percent, P = 0.17). Bivalirudin was at least as effective as high-dose heparin in preventing ischemic complications in patients who underwent angioplasty for unstable angina, and it carried a lower risk of bleeding. Bivalirudin, as compared with heparin, reduced the risk of immediate ischemic complications in patients with postinfarction angina, but this difference was no longer apparent after six months.

                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                April 2001
                13 April 2001
                : 38
                : 2
                : 144-152
                Departments of Internal Medicine and Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
                51041 J Vasc Res 2001;38:144–152
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 4, Tables: 2, References: 29, Pages: 9
                Research Paper


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