Human thrombin receptor‐activating peptide‐induced proliferation of cultured vascular smooth muscle cells exhibits species specificity

Thrombin receptor stimulation in vitro signals many cellular events that are associated with the response to vascular injury in vivo. Indeed, we have previously shown that human α‐thrombin and the 14‐amino acid human thrombin receptor‐activating peptide (huTRAP‐14) stimulate proliferation of cultured rat aortic smooth muscle cells (SMC). In the present studies, the mitogenic response of rabbit vascular SMC to thrombin and huTRAP‐14 was assessed using [3H]thymidine incorporation and cell number. Results demonstrated that thrombin stimulated mitogenesis of rabbit vascular SMC in culture and that the thrombin response was dependent on proteolytic activity. However, huTRAP‐14 was not mitogenic for rabbit vascular SMC. Thus, there are species differences in huTRAP‐14 responsiveness. As rat and rabbit models continue to be used extensively to evaluate mechanisms and potential therapies for human restenosis, it is important to identify any species differences in the mechanism whereby thrombin exerts its biological effects. © 1995 Wiley‐Liss, Inc.

[1]  R. Nutt,et al.  Species Variability in Platelet and other Cellular Responsiveness to Thrombin Receptor-derived Peptides , 1994, Thrombosis and Haemostasis.

[2]  S. Coughlin,et al.  Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. , 1993, The Journal of clinical investigation.

[3]  A. Malik,et al.  Thrombin receptor 14-amino acid peptide mediates endothelial hyperadhesivity and neutrophil adhesion by P-selectin-dependent mechanism. , 1992, Circulation research.

[4]  M. Runge,et al.  Molecular cloning of the rat vascular smooth muscle thrombin receptor. Evidence for in vitro regulation by basic fibroblast growth factor. , 1992, The Journal of biological chemistry.

[5]  M. Hollenberg,et al.  Action of thrombin receptor polypeptide in gastric smooth muscle: identification of a core pentapeptide retaining full thrombin-mimetic intrinsic activity. , 1992, Molecular pharmacology.

[6]  J. Maraganore,et al.  Essential groups in synthetic agonist peptides for activation of the platelet thrombin receptor. , 1992, Biochemistry.

[7]  V. Wheaton,et al.  Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. , 1992, The Journal of biological chemistry.

[8]  T. Ryan,et al.  The effect of antiplatelet therapy on platelet accumulation after experimental angioplasty in the rabbit iliac model. , 1992, International journal of cardiology.

[9]  M. Robson,et al.  Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides. , 1992, The Journal of clinical investigation.

[10]  J. Herbert,et al.  Induction of vascular smooth muscle cell growth by selective activation of the thrombin receptor Effect of heparin , 1992, FEBS letters.

[11]  L. Brass,et al.  Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. , 1992, The Journal of biological chemistry.

[12]  S. Coughlin,et al.  Thrombin-induced events in non-platelet cells are mediated by the unique proteolytic mechanism established for the cloned platelet thrombin receptor , 1992, The Journal of cell biology.

[13]  J P Lecocq,et al.  Synthetic alpha-thrombin receptor peptides activate G protein-coupled signaling pathways but are unable to induce mitogenesis. , 1992, Molecular biology of the cell.

[14]  V. Wheaton,et al.  Domains specifying thrombin–receptor interaction , 1991, Nature.

[15]  J. Pouysségur,et al.  cDNA cloning and expression of a hamster α‐thrombin receptor coupled to Ca2+ mobilization , 1991 .

[16]  W. Roberts,et al.  Effectiveness of Recombinant Desulphatohirudin in Reducing Restenosis After Balloon Angioplasty of Atherosclerotic Femoral Arteries in Rabbits , 1991, Circulation.

[17]  V. Wheaton,et al.  Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation , 1991, Cell.

[18]  M. Nobuyoshi,et al.  Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients. , 1991, Journal of the American College of Cardiology.

[19]  K. Karsch,et al.  Time course of smooth muscle cell proliferation in the intima and media of arteries following experimental angioplasty. , 1990, Circulation research.

[20]  H. Baumgartner,et al.  The proliferative response to vascular injury is suppressed by angiotensin-converting enzyme inhibition. , 1990, Journal of cardiovascular pharmacology.

[21]  M. Nobuyoshi,et al.  Thrombus formation on the aorta injured by angioplasty and its prevention with dilazep in atherosclerotic rabbits. , 1989, Thrombosis research.

[22]  G. Roubin,et al.  Histopathologic phenomena at the site of percutaneous transluminal coronary angioplasty: the problem of restenosis. , 1989, Human pathology.

[23]  G. Owens,et al.  Expression of smooth muscle-specific alpha-isoactin in cultured vascular smooth muscle cells: relationship between growth and cytodifferentiation , 1986, The Journal of cell biology.

[24]  V. Fuster,et al.  Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model. , 1985, Circulation research.

[25]  S. Kelsey,et al.  Long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA): report from the National Heart, Lung, and Blood Institute PTCA Registry. , 1984, The American journal of cardiology.

[26]  K. Glenn,et al.  Thrombin active site regions required for fibroblast receptor binding and initiation of cell division. , 1980, The Journal of biological chemistry.