Coronary artery in-stent stenosis persists despite inhibition of the von Willebrand factor - collagen interaction in baboons

被引:14
作者
De Meyer, Simon F. [1 ]
Staelens, Stephanie [1 ]
Badenhorst, Philip N. [2 ,3 ]
Pieters, Henry [2 ,3 ]
Lamprecht, Seb [2 ,3 ]
Roodt, Jan [2 ,3 ]
Janssens, Stefan
Meiring, Muriel [2 ,3 ]
Vanhoorelbeke, Karen [1 ]
Bruwer, Andre [4 ]
Brown, Stephen [4 ]
Deckmyn, Hans [1 ]
机构
[1] IRC, Lab Thrombosis Res, B-8500 Kortrijk, Belgium
[2] Univ Free State, Dept Haematol & Cell Biol, Bloemfontein, South Africa
[3] Univ Free State, Dept Paediat & Child Hlth, Bloemfontein, South Africa
[4] Katholieke Univ Leuven, Dept Cardiol, Louvain, Belgium
关键词
vonWillebrand factor; stenosis; baboon model; stent; neointima;
D O I
10.1160/TH07-05-0335
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Revascularization techniques, such as angioplasty and stent implantation, frequently lead to restenosis due to the formation of neointima after platelet activation and the concomittant release of various smooth muscle cell mitogenic and attractant factors. We here investigate whether inhibition of initial platelet adhesion after stent implantation can decrease neointima formation in a clinically relevant baboon model of in-stent stenosis using standard treatment with aspirin, clopidogrel and heparin. Inhibition of platelet adhesion was established by administration of the anti-von Willebrand factor (VWF) monoclonal antibody 82D6A3, which inhibits VWF binding to collagen. Administration of 82D6A3 resulted in a complete inhibition of VWF binding to collagen during the first three days after stent implantation. No thrombocytopenia or prolongation of the bleeding time was observed. Our results show that the formation of neointima was not affected in the group of baboons where primary platelet adhesion was abolished with 82D6A3 when compared to the control group. Vascular injury scores were the same in both groups. Inhibition of platelet adhesion during the first three days after stenting, on top of standard treatment with aspirin, clopidogrel and heparin, had no effect on neo-intima formation in a baboon model of in-stent stenosis. During the last decade, attempts to translate seemingly effective therapies based on smaller animal experimentation to the clinic have consistently failed.This study, using a non-human primate model that more closely resembles the clinical situation, presents a model that may be of further clinical interest for studying the prevention of restenosis.
引用
收藏
页码:1343 / 1349
页数:7
相关论文
共 43 条
[21]   Inhibition of von Willebrand factor binding to platelet GP Ib by a fractionated aurintricarboxylic acid prevents restenosis after vascular injury in hamster carotid artery [J].
Matsuno, H ;
Kozawa, O ;
Niwa, M ;
Uematsu, T .
CIRCULATION, 1997, 96 (04) :1299-1304
[22]   A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. [J].
Morice, M ;
Serruys, PW ;
Sousa, JE ;
Fajadet, J ;
Hayashi, EB ;
Perin, M ;
Colombo, A ;
Schuler, G ;
Barragan, P ;
Guagliumi, G ;
Molnar, F ;
Falotico, R .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (23) :1773-1780
[23]   Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery [J].
Moses, JW ;
Leon, MB ;
Popma, JJ ;
Fitzgerald, PJ ;
Holmes, DR ;
O'Shaughnessy, C ;
Caputo, RP ;
Kereiakes, DJ ;
Williams, DO ;
Teirstein, PS ;
Jaeger, JL ;
Kuntz, RE .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (14) :1315-1323
[24]   Antiproliferative agents alter vascular plasminogen activator inhibitor-1 expression - A potential prothrombotic mechanism of drug-eluting stents [J].
Muldowney, James A. S., III ;
Stringham, John R. ;
Levy, Shawn E. ;
Gleaves, Linda A. ;
Eren, Mesut ;
Piana, Robert N. ;
Vaughan, Douglas E. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2007, 27 (02) :400-406
[25]   EXPERIMENTAL-MODELS OF CORONARY-ARTERY RESTENOSIS [J].
MULLER, DWM ;
ELLIS, SG ;
TOPOL, EJ .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1992, 19 (02) :418-432
[26]   Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction [J].
Neumann, FJ ;
Blasini, R ;
Schmitt, C ;
Alt, E ;
Dirschinger, J ;
Gawaz, M ;
Kastrati, A ;
Schömig, A .
CIRCULATION, 1998, 98 (24) :2695-2701
[27]  
PHILLIPS MD, 1988, BLOOD, V72, P1898
[28]   RESTENOSIS AND THE PROPORTIONAL NEOINTIMAL RESPONSE TO CORONARY-ARTERY INJURY - RESULTS IN A PORCINE MODEL [J].
SCHWARTZ, RS ;
HUBER, KC ;
MURPHY, JG ;
EDWARDS, WD ;
CAMRUD, AR ;
VLIETSTRA, RE ;
HOLMES, DR .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1992, 19 (02) :267-274
[29]   Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis [J].
Sinnaeve, P ;
Chiche, JD ;
Gillijins, H ;
Van Pelt, N ;
Wirthlin, D ;
Van de Werf, F ;
Collen, D ;
Bloch, KD ;
Janssens, S .
CIRCULATION, 2002, 105 (24) :2911-2916
[30]   Paratope determination of the antithrombotic antibody 82D6A3 based on the crystal structure of its complex with the von Willebrand factor A3-domain [J].
Staelens, S ;
Hadders, MA ;
Vauterin, S ;
Platteau, C ;
De Maeyer, M ;
Vanhoorelbeke, K ;
Huizinga, EG ;
Deckmyn, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (04) :2225-2231