New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology.

Thrombin is a serine protease that potently activates platelets and catalyzes the conversion of fibrinogen to fibrin. Thrombin also exerts direct effects on vascular cells, such as smooth muscle cells, via interactions with members of the protease-activated receptor family. Evidence in several animal models implicates thrombin-mediated signaling events in the response to injury that typifies vascular lesion formation in atherosclerosis and restenosis. In this review, we examine the activation of protease-activated receptors by thrombin, the downstream signaling events mediated by these receptors, and the physiological role of thrombin in vascular cells and vascular disease.

[1]  W. Arts,et al.  Cerebral thromboembolism due to antithrombin III deficiency in two children. , 1987, Neuropediatrics.

[2]  M. Nishida,et al.  G alpha(i) and G alpha(o) are target proteins of reactive oxygen species. , 2000, Nature.

[3]  M. D'Andrea,et al.  Altered vascular injury responses in mice deficient in protease-activated receptor-1. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

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

[5]  S. Goto,et al.  Plasma Concentration of von Willebrand Factor in Acute Myocardial Infarction , 2000, Thrombosis and Haemostasis.

[6]  Robert Huber,et al.  The refined 1.9 A crystal structure of human alpha‐thrombin: interaction with D‐Phe‐Pro‐Arg chloromethylketone and significance of the Tyr‐Pro‐Pro‐Trp insertion segment. , 1989 .

[7]  T. Michel,et al.  Expression of constitutive endothelial nitric oxide synthase in human blood platelets. , 1995, Life sciences.

[8]  S. J. Taylor,et al.  Activation of the beta 1 isozyme of phospholipase C by alpha subunits of the Gq class of G proteins. , 1991, Nature.

[9]  P. Mannucci,et al.  Inherited thrombophilia: pathogenesis, clinical syndromes, and management. , 1996, Blood.

[10]  G. Stouffer,et al.  Thrombin-induced mitogenesis of vascular SMC is partially mediated by autocrine production of PDGF-AA. , 1993, The American journal of physiology.

[11]  J. Stamler,et al.  Reduced thiols and the effect of intravenous nitroglycerin on platelet aggregation. , 1988, The American journal of cardiology.

[12]  J. Landry,et al.  Transient activation of a distinct serine protein kinase is responsible for 27-kDa heat shock protein phosphorylation in mitogen-stimulated and heat-shocked cells. , 1993, The Journal of biological chemistry.

[13]  J. Stamler,et al.  Effect of nitric oxide synthase inhibition on bleeding time in humans. , 1995, Journal of cardiovascular pharmacology.

[14]  D. Lawrence,et al.  Plasminogen Activator Inhibitor-1 and Vitronectin Promote the Cellular Clearance of Thrombin by Low Density Lipoprotein Receptor-related Proteins 1 and 2 (*) , 1996, The Journal of Biological Chemistry.

[15]  S. Hoshino,et al.  Heterodimeric Phosphoinositide 3-Kinase Consisting of p85 and p110β Is Synergistically Activated by the βγ Subunits of G Proteins and Phosphotyrosyl Peptide* , 1997, The Journal of Biological Chemistry.

[16]  P. Morris,et al.  The factor V Leiden (R506Q) mutation and risk of thrombosis in renal transplant recipients. , 1997, Transplantation.

[17]  R W Alexander,et al.  Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. , 1994, Circulation research.

[18]  G. Owens,et al.  Local Adenovirus-Mediated Delivery of Hirudin in a Rabbit Arterial Injury Model , 1999, Journal of Vascular Research.

[19]  C. Esmon,et al.  Recurrent venous thromboembolism in patients with a partial deficiency of protein S. , 1984, The New England journal of medicine.

[20]  A. Buchwald,et al.  Inhibition of neointimal proliferation after coronary angioplasty by low-molecular-weight heparin (clivarine) and polyethyleneglycol-hirudin. , 1996, Journal of cardiovascular pharmacology.

[21]  A. Horrevoets,et al.  The suicide substrate reaction between plasminogen activator inhibitor 1 and thrombin is regulated by the cofactors vitronectin and heparin. , 1997, Blood.

[22]  José A López,et al.  Molecular mechanisms of platelet adhesion and activation. , 1997, The international journal of biochemistry & cell biology.

[23]  S. Coughlin,et al.  Protease-activated receptor 3 is a second thrombin receptor in humans , 1997, Nature.

[24]  S. Moncada,et al.  Comparative pharmacology of endothelium‐derived relaxing factor, nitric oxide and prostacyclin in platelets , 1987, British journal of pharmacology.

[25]  J. Loscalzo,et al.  Inhibition of fibrinogen binding to human platelets by S-nitroso-N-acetylcysteine. , 1990, The Journal of biological chemistry.

[26]  A. Lumsden,et al.  Characterization of thrombin receptor expression during vascular lesion formation. , 1994, Circulation research.

[27]  R. Chambers,et al.  Thrombin Stimulates Smooth Muscle Cell Procollagen Synthesis and mRNA Levels via a PAR-1 Mediated Mechanism , 1998, Thrombosis and Haemostasis.

[28]  R. Huber,et al.  The refined 1.9 A crystal structure of human alpha‐thrombin: interaction with D‐Phe‐Pro‐Arg chloromethylketone and significance of the Tyr‐Pro‐Pro‐Trp insertion segment. , 1989, The EMBO journal.

[29]  D. Wagner,et al.  Pro-coagulant state resulting from high levels of soluble P-selectin in blood. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Maglott,et al.  The Human Proteinase-activated Receptor-3 (PAR-3) Gene , 1998, The Journal of Biological Chemistry.

[31]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[32]  A. Malik,et al.  Regulation of vascular endothelial barrier function. , 1994, The American journal of physiology.

[33]  S. Moncada,et al.  ENDOGENOUS NITRIC OXIDE INHIBITS HUMAN PLATELET ADHESION TO VASCULAR ENDOTHELIUM , 1987, The Lancet.

[34]  A. Chaouat,et al.  The role of thrombosis in severe pulmonary hypertension. , 1996, The European respiratory journal.

[35]  P. Parker,et al.  Characterization and partial purification of a novel neutrophil membrane-associated kinase capable of phosphorylating the respiratory burst component p 47 phox , 1999 .

[36]  G. Owens,et al.  A new single-injury model of balloon angioplasty in cholesterol-fed rabbits: beneficial effect of hirudin and comparison with double-injury model. , 1997, Laboratory investigation; a journal of technical methods and pathology.

[37]  P. Carmeliet,et al.  Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation: a gene targeting and gene transfer study in mice. , 1997, Circulation.

[38]  E. Topol,et al.  Influence of blockade at specific levels of the coagulation cascade on restenosis in a rabbit atherosclerotic femoral artery injury model. , 1995, Circulation.

[39]  R. Cohen,et al.  Nitric Oxide Inhibits Capacitative Cation Influx in Human Platelets by Promoting Sarcoplasmic / Endoplasmic Reticulum Ca 2 1-ATPase – Dependent Refilling of Ca 2 1 Stores , 1999 .

[40]  F. Murad,et al.  Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. , 1977, Journal of cyclic nucleotide research.

[41]  P. A. Peterson,et al.  Biological Consequences of Thrombin Receptor Deficiency in Mice , 1996, Thrombosis and Haemostasis.

[42]  Harold Roberts,et al.  Hypercoagulability in Venous and Arterial Thrombosis , 1997, Annals of Internal Medicine.

[43]  Y. Suh,et al.  Cell transformation by the superoxide-generating oxidase Mox1 , 1999, Nature.

[44]  J. Stamler,et al.  Synergistic Disaggregation of Platelets by Tissue-Type Plasminogen Activator, Prostaglandin El9 and Nitroglycerin , 1989, Circulation research.

[45]  J. Stamler,et al.  Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[46]  E. Fishman,et al.  Abdominal pain in sickle cell disease: the role of CT. , 1987, Radiology.

[47]  Jacqueline P Mitchell,et al.  Comparison of Novel Hemostatic Factors and Conventional Risk Factors for Prediction of Coronary Heart Disease , 2000, Circulation.

[48]  K. Walsh,et al.  Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. , 2000, Circulation research.

[49]  W. Aird,et al.  Targeting of transgene expression to the vascular endothelium of mice by homologous recombination at the thrombomodulin locus. , 1996, Circulation research.

[50]  J. Ando,et al.  Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells. , 1994, Biochemical and biophysical research communications.

[51]  P. Serruys,et al.  A comparison of hirudin with heparin in the prevention of restenosis after coronary angioplasty. Helvetica Investigators. , 1995, The New England journal of medicine.

[52]  D. Collen,et al.  Nitric oxide inhalation inhibits platelet aggregation and platelet-mediated pulmonary thrombosis in rats. , 1997, Circulation research.

[53]  W. Morain,et al.  Cellular Localization of Enzymatically Active Thrombin in Intact Human Tissues by Hirudin Binding , 1995, Thrombosis and Haemostasis.

[54]  H Harasaki,et al.  eNOS-overexpressing endothelial cells inhibit platelet aggregation and smooth muscle cell proliferation in vitro. , 2000, Tissue engineering.

[55]  J. Maraganore,et al.  Effectiveness of hirulog in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. , 1996, Journal of vascular research.

[56]  H. Markus,et al.  Genetics and ischaemic stroke. , 2000, Brain : a journal of neurology.

[57]  L. Marnett,et al.  Characterization of the hydroperoxide-reducing activity of human plasma. , 1987, Archives of biochemistry and biophysics.

[58]  U. Lindahl,et al.  Glycosaminoglycans and the regulation of blood coagulation. , 1993, The Biochemical journal.

[59]  H. Drexler,et al.  G protein-coupled receptors control vascular smooth muscle cell proliferation via pp60c-src and p21ras. , 1997, The American journal of physiology.

[60]  Robert V Farese,et al.  Role of the thrombin receptor in development and evidence for a second receptor , 1996, Nature.

[61]  P. Huang,et al.  Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. , 1999, Circulation research.

[62]  R. Marlar,et al.  Coagulation and fibrinolytic profiles in patients with severe pulmonary hypertension. , 1996, Chest.

[63]  H. Rayburn,et al.  A targeted point mutation in thrombomodulin generates viable mice with a prethrombotic state. , 1998, The Journal of clinical investigation.

[64]  J. Loscalzo,et al.  Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis. , 1996, The Journal of clinical investigation.

[65]  T W Gardner,et al.  Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties. , 2000, Microvascular research.

[66]  M. Kelm Nitric oxide metabolism and breakdown. , 1999, Biochimica et biophysica acta.

[67]  M. Bennett,et al.  Thrombin generation by apoptotic vascular smooth muscle cells. , 1997, Blood.

[68]  Robert V Farese,et al.  A dual thrombin receptor system for platelet activation , 1998, Nature.

[69]  E. Jaffe,et al.  Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. , 1997, Blood.

[70]  A. Baker,et al.  Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis. , 1998, The Journal of clinical investigation.

[71]  S. Barnes,et al.  Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. , 1994, The Journal of biological chemistry.

[72]  Y. Tohyama,et al.  Translocation, activation and association of protein-tyrosine kinase (p72syk) with phosphatidylinositol 3-kinase are early events during platelet activation. , 1994, European journal of biochemistry.

[73]  C. Benjamin,et al.  Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets , 1992, Nature.

[74]  J. Loscalzo,et al.  The potent platelet inhibitory effects of S-nitrosated albumin coating of artificial surfaces. , 1999, Journal of the American College of Cardiology.

[75]  G. Bokoch,et al.  G Protein-coupled Chemoattractant Receptors Regulate Lyn Tyrosine Kinase·Shc Adapter Protein Signaling Complexes (*) , 1995, The Journal of Biological Chemistry.

[76]  W. Bell,et al.  Thrombotic Thrombocytopenic Purpura: Report of 25 Cases and Review of the Literature , 1981, Medicine.

[77]  E. Kruithof,et al.  Expression of LDL receptor-related protein/alpha 2-macroglobulin receptor in human normal and atherosclerotic arteries. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[78]  M. Runge,et al.  The oxidative paradox: another piece in the puzzle. , 2000, Circulation research.

[79]  T. Ortel,et al.  Clinical and laboratory evaluation of the hypercoagulable states. , 1995, Clinics in chest medicine.

[80]  I. Russo,et al.  L-arginine modulates aggregation and intracellular cyclic 3,5-guanosine monophosphate levels in human platelets: direct effect and interplay with antioxidative thiol agent. , 1999, Thrombosis research.

[81]  S. Yoshitake,et al.  Antibody to thrombin receptor inhibits neointimal smooth muscle cell accumulation without causing inhibition of platelet aggregation or altering hemostatic parameters after angioplasty in rat. , 1998, Circulation research.

[82]  M. Ushio-Fukai,et al.  p22phox Is a Critical Component of the Superoxide-generating NADH/NADPH Oxidase System and Regulates Angiotensin IIinduced Hypertrophy in Vascular Smooth Muscle Cells* , 1996, The Journal of Biological Chemistry.

[83]  T. Katada,et al.  Activation of PI 3-kinase by G protein βγ subunits , 1998 .

[84]  Z. Liu,et al.  S-Transnitrosation reactions are involved in the metabolic fate and biological actions of nitric oxide. , 1998, The Journal of pharmacology and experimental therapeutics.

[85]  R. Rosenberg Biochemistry of heparin antithrombin interactions, and the physiologic role of this natural anticoagulant mechanism. , 1989, The American journal of medicine.

[86]  S. Schwartz,et al.  Regulation of platelet-derived growth factor ligand and receptor gene expression by alpha-thrombin in vascular smooth muscle cells. , 1992, Circulation research.

[87]  S. Moncada,et al.  Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty , 1994, The Lancet.

[88]  K. Hajjar,et al.  Annexin II and Regulation of Cell Surface Fibrinolysis , 2000, Annals of the New York Academy of Sciences.

[89]  P. Libby,et al.  Thrombin potently stimulates cytokine production in human vascular smooth muscle cells but not in mononuclear phagocytes. , 1996, Circulation research.

[90]  V. Marder,et al.  Tissue factor mRNA expression in the endothelium of an intact umbilical vein. , 1996, Blood.

[91]  G. Owens,et al.  Arterial thrombin activity after angioplasty in an atherosclerotic rabbit model: time course and effect of hirudin. , 1996, Circulation.

[92]  W. Aird,et al.  Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression. , 2000, Physiological genomics.

[93]  M. Richardson,et al.  Deendothelialization in vivo initiates a thrombogenic reaction at the rabbit aorta surface. Correlation of uptake of fibrinogen and antithrombin III with thrombin generation by the exposed subendothelium. , 1989, The American journal of pathology.

[94]  M. Runge,et al.  Thrombin Regulates Vascular Smooth Muscle Cell Growth and Heat Shock Proteins via the JAK-STAT Pathway* , 2001, The Journal of Biological Chemistry.

[95]  K.,et al.  Homozygous Antithrombin Deficiency: Report of Two New Cases (99 Leu to Phe) Associated with Arterial and Venous Thrombosis , 1994, Thrombosis and Haemostasis.

[96]  R. Nutt,et al.  An antibody against the exosite of the cloned thrombin receptor inhibits experimental arterial thrombosis in the African green monkey. , 1995, Circulation.

[97]  E. Jaffe,et al.  The correlation between rises in intracellular calcium and PGI2 production in cultured vascular endothelial cells. , 1992, Prostaglandins, leukotrienes, and essential fatty acids.

[98]  J. Abraham,et al.  Heparin blockade of thrombin-induced smooth muscle cell migration involves inhibition of epidermal growth factor (EGF) receptor transactivation by heparin-binding EGF-like growth factor. , 2000, Circulation research.

[99]  M. Greaves,et al.  The hypercoagulable state in clinical practice. , 1991, British journal of haematology.

[100]  K Walsh,et al.  Evidence for the rapid onset of apoptosis in medial smooth muscle cells after balloon injury. , 1997, Circulation.

[101]  D. Mahoney,et al.  Functional Deficiency of Protein C Associated with Mesenteric Venous Thrombosis and Splenic Infarction , 1991, American Journal Of Pediatric Hematology/Oncology.

[102]  J. Griffin,et al.  Deficiency of protein C in congenital thrombotic disease. , 1981, The Journal of clinical investigation.

[103]  S. Coughlin Protease-Activated Receptors and Platelet Function , 1999, Thrombosis and Haemostasis.

[104]  RoyG. Smith,et al.  Hereditary spherocytosis, thrombocytosis, and chronic pulmonary emboli: A case report and review of the literature , 1998, American journal of hematology.

[105]  A. Ahlbom,et al.  Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[106]  R. Bartlett,et al.  Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers , 2000, Critical care medicine.

[107]  K. Nomoto,et al.  Regulation of Vascular Smooth Muscle Cell Proliferation by Nuclear Factor-κB and Its Inhibitor, I-κB* , 2000, The Journal of Biological Chemistry.

[108]  F. Church,et al.  Altered Dermatan Sulfate Structure and Reduced Heparin Cofactor II-stimulating Activity of Biglycan and Decorin from Human Atherosclerotic Plaque* , 2000, The Journal of Biological Chemistry.

[109]  J. Sixma,et al.  Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis. , 1997, Stroke.

[110]  M. Oppermann,et al.  Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells attenuates mitogenic signaling via G protein-coupled and platelet-derived growth factor receptors. , 2000, Circulation.

[111]  N. Tsopanoglou,et al.  Thrombin promotes angiogenesis by a mechanism independent of fibrin formation. , 1993, The American journal of physiology.

[112]  G. Rao,et al.  Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. , 1992, Circulation research.

[113]  L. Ignarro,et al.  Evidence for the inhibitory role of guanosine 3', 5'-monophosphate in ADP-induced human platelet aggregation in the presence of nitric oxide and related vasodilators. , 1981, Blood.

[114]  J. Pouysségur,et al.  Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells. , 2000, The Journal of biological chemistry.

[115]  R. Johns Endothelium-derived relaxing factor: basic review and clinical implications. , 1991, Journal of cardiothoracic and vascular anesthesia.

[116]  J. Brown,et al.  Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration. , 1999, Circulation research.

[117]  J. Loscalzo,et al.  Plasma glutathione peroxidase deficiency and platelet insensitivity to nitric oxide in children with familial stroke. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[118]  J. Stamler,et al.  Intravenous Nitroglycerin Infusion Inhibits Cyclic Blood Flow Responses Caused by Periodic Platelet Thrombus Formation in Stenosed Canine Coronary Arteries , 1991, Circulation.

[119]  M. Bond,et al.  Differential distribution of 70-kD heat shock protein in atherosclerosis. Its potential role in arterial SMC survival. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[120]  N. Tsopanoglou,et al.  On the Mechanism of Thrombin-induced Angiogenesis , 1999, The Journal of Biological Chemistry.

[121]  J. Loscalzo,et al.  N-Acetylcysteine potentiates inhibition of platelet aggregation by nitroglycerin. , 1985, The Journal of clinical investigation.

[122]  K. Takatsuki,et al.  Homozygous Variant of Antithrombin III that Lacks Affinity for Heparin, AT III Kumamoto , 1989, Thrombosis and Haemostasis.

[123]  B. Sobel,et al.  Vascular smooth muscle cell migration mediated by thrombin and urokinase receptor. , 1995, The American journal of physiology.

[124]  P. Parker,et al.  Characterization and partial purification of a novel neutrophil membrane-associated kinase capable of phosphorylating the respiratory burst component p47phox. , 1999, The Biochemical journal.

[125]  J. Loscalzo,et al.  Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide. , 1995, The Journal of clinical investigation.

[126]  R. Jackman,et al.  Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress. , 1994, Circulation research.

[127]  S. Wohlfeil,et al.  Comparison of the effects of the thrombin inhibitor r-hirudin in four animal models of neointima formation after arterial injury. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[128]  William Arbuthnot Sir Lane,et al.  Antiangiogenic activity of the cleaved conformation of the serpin antithrombin. , 1999, Science.

[129]  B. Berk,et al.  Endothelial NO synthase is increased in regenerating endothelium after denuding injury of the rat aorta. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[130]  L. Ignarro,et al.  Endothelium‐Derived Relaxing Factor From Pulmonary Artery and Vein Possesses Pharmacologic and Chemical Properties Identical to Those of Nitric Oxide Radical , 1987, Circulation research.

[131]  H. Lander An essential role for free radicals and derived species in signal transduction , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[132]  S. Rafii,et al.  Constitutive production and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[133]  E. Bassenge Antiplatelet effects of endothelium-derived relaxing factor and nitric oxide donors. , 1991, European heart journal.

[134]  K. Preissner,et al.  Differences in coagulant and fibrinolytic activities of cultured human endothelial cells derived from omental tissue microvessels and umbilical veins. , 1987, Blood.

[135]  W. Aird,et al.  PDGF mediates cardiac microvascular communication. , 1998, The Journal of clinical investigation.

[136]  C. Wahlestedt,et al.  Molecular cloning of a potential proteinase activated receptor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[137]  M. Crow,et al.  The inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alphavbeta3 integrin complex is reversed by activated calcium/calmodulin- dependent protein kinase II. , 1997, The Journal of clinical investigation.

[138]  F. Lupu,et al.  Colocalization of thrombin, PAI-1, and vitronectin in the atherosclerotic vessel wall: A potential regulatory mechanism of thrombin activity by PAI-1/vitronectin complexes. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[139]  D. Turk,et al.  The refined 1.9‐Å X‐ray crystal structure of d‐Phe‐Pro‐Arg chloromethylketone‐inhibited human α‐thrombin: Structure analysis, overall structure, electrostatic properties, detailed active‐site geometry, and structure‐function relationships , 1992, Protein science : a publication of the Protein Society.

[140]  P. Liaw,et al.  Comparison of Heparin- and Dermatan Sulfate-mediated Catalysis of Thrombin Inactivation by Heparin Cofactor II* , 1999, The Journal of Biological Chemistry.

[141]  N. Yanagisawa,et al.  Soluble Form of Selectins in Blood of Patients with Acute Myocardial Infarction and Coronary Intervention , 1997, Vascular medicine.

[142]  M. Zabinski,et al.  Thrombin Noncovalent-Protein Binding And Fibrin(Ogen) Recognition , 1981, Thrombosis and Haemostasis.

[143]  A. Ullrich,et al.  Role of transactivation of the EGF receptor in signalling by G-protein-coupled receptors , 1996, Nature.

[144]  J P Cooke,et al.  Flow stimulates endothelial cells to release a nitrovasodilator that is potentiated by reduced thiol. , 1990, The American journal of physiology.

[145]  M. Runge,et al.  Thrombin hypothesis of thrombus generation and vascular lesion formation. , 1995, The American journal of cardiology.

[146]  J. Loscalzo,et al.  Effects of nitric oxide/EDRF on platelet surface glycoproteins. , 1996, The American journal of physiology.

[147]  M. Hollenberg,et al.  Proteinase-activated receptor 4 (PAR4): action of PAR4-activating peptides in vascular and gastric tissue and lack of cross-reactivity with PAR1 and PAR2. , 1999, Canadian journal of physiology and pharmacology.

[148]  S. Moncada,et al.  Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor , 1987, Nature.

[149]  J. Freedman,et al.  α‐Tocopherol and protein kinase C inhibition enhance platelet‐derived nitric oxide release , 2000 .

[150]  G. Davı̀,et al.  Homocysteine, Coagulation, Platelet Function, and Thrombosis , 2000, Seminars in thrombosis and hemostasis.

[151]  M. J. Giddings,et al.  Subcutaneous infusion of r‐hirudin does not inhibit neointimal proliferation after angioplasty of the subclavian artery in cholesterol‐fed rabbits , 1996, Coronary artery disease.

[152]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[153]  J. Stamler,et al.  In vivo transfer of nitric oxide between a plasma protein-bound reservoir and low molecular weight thiols. , 1994, The Journal of clinical investigation.

[154]  G. Hughes,et al.  The “Primary” Antiphospholipid Syndrome: Major Clinical and Serological Features , 1989, Medicine.

[155]  S. Coughlin,et al.  Thrombin signalling and protease-activated receptors , 2000, Nature.

[156]  C. Kanthou,et al.  Thrombin‐induced proliferation and expression of platelet‐derived growth factor‐A chain gene in human vascular smooth muscle cells , 1992, FEBS letters.

[157]  J. Loscalzo,et al.  S-Nitrosoderivative of a Recombinant Fragment of von Willebrand Factor (S-Nitroso-AR545C) Inhibits Thrombus Formation in Guinea Pig Carotid Artery Thrombosis Model , 2000, Thrombosis and Haemostasis.

[158]  J. Cooper,et al.  Increased Activation of the Haemostatic System in Men at High Risk of Fatal Coronary Heart Disease , 1996, Thrombosis and Haemostasis.

[159]  J. Mary,et al.  Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors , 1996, The Lancet.

[160]  G. Schultz,et al.  G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[161]  M. Raida,et al.  Inhibition of platelet aggregation by S‐nitroso‐cysteine via cGMP‐independent mechanisms: evidence of inhibition of thromboxane A2 synthesis in human blood platelets , 1999, FEBS letters.

[162]  J. Hothersall,et al.  S-nitrosothiols are stored by platelets and released during platelet-neutrophil interactions. , 1999, Nitric oxide : biology and chemistry.

[163]  A. Marcus,et al.  Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39. , 1998, The Journal of clinical investigation.

[164]  A. Jaffe,et al.  Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. , 1990, Circulation.

[165]  P. Hufnagl,et al.  Type 1 plasminogen activator inhibitor synthesis of endothelial cells is downregulated by smooth muscle cells. , 1993, Blood.

[166]  C. Bode,et al.  Stimulation of a Vascular Smooth Muscle Cell NAD(P)H Oxidase by Thrombin , 1999, The Journal of Biological Chemistry.

[167]  P. Delafontaine,et al.  G-protein coupled and tyrosine kinase receptors: evidence that activation of the insulin-like growth factor I receptor is required for thrombin-induced mitogenesis of rat aortic smooth muscle cells. , 1996, The Journal of clinical investigation.

[168]  M. Runge,et al.  Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[169]  N. Prévost,et al.  Thrombin Responses in Human Endothelial Cells , 2000, The Journal of Biological Chemistry.

[170]  P. Carmeliet,et al.  Physiological consequences of loss of plasminogen activator gene function in mice , 1994, Nature.

[171]  D. Normandin,et al.  Involvement of the "tethered ligand" receptor in thrombin-induced endothelium-mediated relaxations. , 1993, The American journal of physiology.

[172]  H. Jiang,et al.  Diffusion of peroxynitrite into the human platelet inhibits cyclooxygenase via nitration of tyrosine residues. , 2000, The Journal of pharmacology and experimental therapeutics.

[173]  Diana A Gorog,et al.  Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process. , 1994, Journal of vascular research.

[174]  J. Loscalzo,et al.  Cell-surface protein disulfide isomerase catalyzes transnitrosation and regulates intracellular transfer of nitric oxide. , 1999, The Journal of clinical investigation.

[175]  David S. Taylor,et al.  Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[176]  P. Sims,et al.  Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. , 1989, The Journal of biological chemistry.

[177]  M. Ginsberg,et al.  The Effect of Nitric Oxide Synthase Inhibition on Acute Platelet Accumulation and Hemodynamic Depression in a Rat Model of Thromboembolic Stroke , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[178]  T. Barbui,et al.  Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. , 1996, The American journal of medicine.

[179]  E. Chilvers,et al.  Phosphatidylinositol 3-kinase mediates mitogen-induced human airway smooth muscle cell proliferation. , 1999, American journal of physiology. Lung cellular and molecular physiology.

[180]  D. Webb,et al.  Inhibition of human platelet aggregation by a novel S‐nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti‐thrombotic therapy , 2000, British journal of pharmacology.

[181]  PietroMinuz,et al.  The F2-Isoprostane 8-Epiprostaglandin F2α Increases Platelet Adhesion and Reduces the Antiadhesive and Antiaggregatory Effects of NO , 1998 .

[182]  D. Loskutoff,et al.  Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. , 1991, The Journal of clinical investigation.

[183]  V. Ferrans,et al.  Requirement for Generation of H2O2 for Platelet-Derived Growth Factor Signal Transduction , 1995, Science.

[184]  R. Virmani,et al.  Local adenoviral–mediated expression of recombinant hirudin reduces neointima formation after arterial injury , 1996, Nature Medicine.

[185]  G. Guidi,et al.  Effects of sodium selenite on in vitro interactions between platelets and endothelial cells , 1999, International journal of clinical & laboratory research.

[186]  J. Folts An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. , 1991, Circulation.

[187]  S. Wickline,et al.  Inhibition of thrombin attenuates stenosis after arterial injury in minipigs. , 1996, Journal of the American College of Cardiology.

[188]  Janice,et al.  Thrombin is an important mediator of platelet aggregation in stenosed canine coronary arteries with endothelial injury. , 1989, The Journal of clinical investigation.

[189]  G. Hughes,et al.  The management of thrombosis in the antiphospholipid-antibody syndrome. , 1995, The New England journal of medicine.

[190]  D. Witte,et al.  Prothrombin deficiency results in embryonic and neonatal lethality in mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[191]  D. Sorescu,et al.  NAD(P)H oxidase: role in cardiovascular biology and disease. , 2000, Circulation research.

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

[193]  G. Owens,et al.  Early plus delayed hirudin reduces restenosis in the atherosclerotic rabbit more than early administration alone: potential implications for dosing of antithrombin agents. , 1998, Circulation.

[194]  K. Mann,et al.  Identification of a thrombin sequence with growth factor activity on macrophages. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[195]  J. Loscalzo,et al.  Glutathione peroxidase potentiates the inhibition of platelet function by S-nitrosothiols. , 1995, The Journal of clinical investigation.

[196]  R. Rubin,et al.  A murine model of myocardial microvascular thrombosis. , 1999, The Journal of clinical investigation.

[197]  J. Burchenal,et al.  Effect of direct thrombin inhibition with Bivalirudin (Hirulog) on restenosis after coronary angioplasty. , 1998, The American journal of cardiology.

[198]  P. Jones,et al.  Regulation of Tenascin-C, a Vascular Smooth Muscle Cell Survival Factor that Interacts with the αvβ3 Integrin to Promote Epidermal Growth Factor Receptor Phosphorylation and Growth , 1997, The Journal of cell biology.

[199]  G. Remuzzi,et al.  The pathophysiology and management of thrombotic thrombocytopenic purpura , 1996, European journal of haematology.

[200]  E. Sacchi,et al.  High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives. , 1998, The New England journal of medicine.

[201]  Stefan Offermanns,et al.  Vascular System Defects and Impaired Cell Chemokinesis as a Result of Gα13 Deficiency , 1997, Science.

[202]  Quansheng Zhou,et al.  Nitric oxide release from resting human platelets. , 1995, Thrombosis research.

[203]  D. Belin,et al.  A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase , 1985, The Journal of cell biology.

[204]  R. Kelly,et al.  Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. , 1993, The Journal of clinical investigation.

[205]  R. Bar-Shavit,et al.  Monocyte chemotaxis: stimulation by specific exosite region in thrombin. , 1983, Science.

[206]  M. Endres,et al.  Atorvastatin Upregulates Type III Nitric Oxide Synthase in Thrombocytes, Decreases Platelet Activation, and Protects From Cerebral Ischemia in Normocholesterolemic Mice , 2000, Stroke.

[207]  J. Loscalzo,et al.  Impaired platelet production of nitric oxide predicts presence of acute coronary syndromes. , 1998, Circulation.

[208]  J. Jesty,et al.  Vascular endothelial groth factor induces tissue factor and matrix metalloproteinase production in endothelial cells: Conversion of prothrombin to thrombin results in progelatininase a activation and cell proliferation , 1998, International journal of cancer.

[209]  S. Orkin,et al.  Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoeitin/MGDF in megakaryocyte development , 1995, Cell.

[210]  R. Huber,et al.  The structure of a complex of recombinant hirudin and human alpha-thrombin. , 1990, Science.

[211]  C. Teng,et al.  Inhibition of platelet adhesion to collagen by cGMP-elevating agents. , 1997, Biochemical and biophysical research communications.

[212]  J. Loscalzo,et al.  Nitric oxide released from activated platelets inhibits platelet recruitment. , 1997, The Journal of clinical investigation.

[213]  J. Stamler,et al.  The antiplatelet effects of organic nitrates and related nitroso compounds in vitro and in vivo and their relevance to cardiovascular disorders. , 1991, Journal of the American College of Cardiology.

[214]  S. Coughlin,et al.  PAR3 is a cofactor for PAR4 activation by thrombin , 2000, Nature.

[215]  R. van Furth,et al.  Growth characteristics of cultured human macrovascular venous and arterial and microvascular endothelial cells. , 1994, Journal of vascular research.

[216]  B. Jahn,et al.  Oxygen radical generation in human platelets: dependence on 12-lipoxygenase activity and on the glutathione cycle. , 1990, International archives of allergy and applied immunology.

[217]  J. Loscalzo,et al.  alpha-tocopherol inhibits aggregation of human platelets by a protein kinase C-dependent mechanism. , 1996, Circulation.

[218]  A. J. Honour,et al.  Platelet behaviour and drugs used in cardiovascular disease. , 1967, Cardiovascular research.

[219]  Scott R. Presnell,et al.  Cloning and characterization of human protease-activated receptor 4. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[220]  M. Petri Management of thrombosis in antiphospholipid antibody syndrome. , 2001, Rheumatic diseases clinics of North America.

[221]  Y. Asada,et al.  Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. , 1985, Thrombosis research.

[222]  C. Esmon,et al.  The roles of protein C and thrombomodulin in the regulation of blood coagulation. , 1984, The Journal of biological chemistry.

[223]  S. Coughlin,et al.  Tissue factor- and factor X-dependent activation of protease-activated receptor 2 by factor VIIa. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[224]  Patricia D. Christie,et al.  Targeted disruption of cd39/ATP diphosphohydrolase results in disordered hemostasis and thromboregulation , 1999, Nature Medicine.

[225]  Che-hung Lee,et al.  LIPOPOLYSACCHARIDE-INDUCED DIFFERENTIAL CELL SURFACE EXPRESSION OF INTERCELLULAR ADHESION MOLECULE-1 IN CULTURED HUMAN UMBILICAL CORD VEIN ENDOTHELIAL CELLS , 1995, Shock.

[226]  Alberto Smith,et al.  A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis. , 1999, Journal of vascular surgery.

[227]  P. Newburger,et al.  Sequences in the 3'-untranslated region of the human cellular glutathione peroxidase gene are necessary and sufficient for selenocysteine incorporation at the UGA codon. , 1993, The Journal of biological chemistry.

[228]  K. Satoh,et al.  Hemodynamic forces modulate the effects of cytokines on fibrinolytic activity of endothelial cells. , 1996, Blood.

[229]  B. Chaitman,et al.  Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. , 1995, The New England journal of medicine.

[230]  A. Marcus,et al.  Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[231]  J. Chan,et al.  Association of plasminogen activator inhibitor-1 4G/4G genotype and type 2 diabetic nephropathy in Chinese patients. , 2000, Kidney international.

[232]  P. Davies,et al.  Flow-mediated endothelial mechanotransduction. , 1995, Physiological reviews.

[233]  J. Degen,et al.  Resolution of spontaneous bleeding events but failure of pregnancy in fibrinogen-deficient mice. , 1995, Genes & development.

[234]  M. Nishida,et al.  Gαi and Gαo are target proteins of reactive oxygen species , 2000, Nature.

[235]  C. Downes,et al.  Biphasic Activation of PKBα/Akt In Platelets , 1998, The Journal of Biological Chemistry.

[236]  V. Fuster,et al.  Prolonged thrombin inhibition reduces restenosis after balloon angioplasty in porcine coronary arteries. , 1998, Circulation.

[237]  A. Barr,et al.  Reconstitution of Receptors and GTP-binding Regulatory Proteins (G Proteins) in Sf9 Cells , 1997, The Journal of Biological Chemistry.

[238]  K. Ogawa,et al.  Comparison of the effects of nitric oxide and peroxynitrite on the 12-lipoxygenase and cyclooxygenase metabolism of arachidonic acid in rabbit platelets. , 1998, Prostaglandins, leukotrienes, and essential fatty acids.

[239]  S. Coughlin,et al.  The cloned platelet thrombin receptor couples to at least two distinct effectors to stimulate phosphoinositide hydrolysis and inhibit adenylyl cyclase. , 1992, The Journal of biological chemistry.

[240]  J. Loscalzo,et al.  Nitric Oxide Inhibits Thrombin Receptor-activating Peptide-induced Phosphoinositide 3-Kinase Activity in Human Platelets* , 1999, The Journal of Biological Chemistry.

[241]  Thiennu H. Vu,et al.  Thrombin receptor expression in normal and atherosclerotic human arteries. , 1992, The Journal of clinical investigation.

[242]  J. Mehta,et al.  Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets. , 1997, American journal of physiology. Heart and circulatory physiology.

[243]  U. Laufs,et al.  Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. , 1998, Circulation.

[244]  F. Sakamaki,et al.  Increased Plasma P-Selectin and Decreased Thrombomodulin in Pulmonary Arterial Hypertension Were Improved by Continuous Prostacyclin Therapy , 2000, Circulation.

[245]  H. Koshiba,et al.  Heparin cofactor II inhibits thrombus formation in a rat thrombosis model. , 2000, Thrombosis research.

[246]  Sanjay S. Srivatsa,et al.  Selective αvβ3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury1 , 1997 .

[247]  G. Welch,et al.  Nitric Oxide and the Cardiovascular System , 2000, Contemporary Cardiology.

[248]  E. B. Smith,et al.  Prothrombin-Related Antigens in Human Aortic Intima , 1996, Seminars in thrombosis and hemostasis.

[249]  M. Wolf,et al.  Homozygous Variant of Antithrombin III : AT III Fontainebleau , 1986, Thrombosis and Haemostasis.

[250]  T. Raghunathan,et al.  Factor V Leiden (resistance to activated protein C) increases the risk of myocardial infarction in young women. , 1997, Blood.

[251]  M. Ratajczak,et al.  Binding of stromal derived factor‐1α(SDF‐1α) to CXCR4 chemokine receptorin normal human megakaryoblasts butnot in platelets induces phosphorylationof mitogen‐activated protein kinase p42/44 (MAPK), ELK‐1 transcription factor and serine/threonine kinase AKT , 2000, European journal of haematology.

[252]  P. Ridker,et al.  Factor V Leiden Mutation and the Risks for Thromboembolic Disease: A Clinical Perspective , 1997, Annals of Internal Medicine.

[253]  R. Weiss,et al.  The mitogenic effect of thrombin in vascular smooth muscle cells is largely due to basic fibroblast growth factor. , 1993, The Journal of biological chemistry.

[254]  T. Murohara,et al.  Platelet-derived nitric oxide and coronary risk factors. , 2000, Hypertension.

[255]  S. Chien,et al.  Shear stress induction of the tissue factor gene. , 1997, The Journal of clinical investigation.

[256]  W. Rosse,et al.  The natural history of paroxysmal nocturnal hemoglobinuria. , 1997, Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion.

[257]  T. Bugge,et al.  Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. , 1995, Genes & development.

[258]  H. Kleinman,et al.  Thrombin promotes endothelial cell alignment in Matrigel in vitro and angiogenesis in vivo. , 1997, The American journal of physiology.

[259]  F. Church,et al.  Heparin cofactor II and thrombin Heparin-binding proteins linking hemostasis and inflammation. , 1994, Trends in cardiovascular medicine.

[260]  TsutomuImaizumi,et al.  Long-term Smoking Impairs Platelet-Derived Nitric Oxide Release , 1996 .

[261]  M. Runge,et al.  Cyclic AMP Inhibition of Thrombin-induced Growth in Vascular Smooth Muscle Cells Correlates with Decreased JNK1 Activity and c-Jun Expression* , 1996, The Journal of Biological Chemistry.

[262]  A. Ullrich,et al.  EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF , 1999, Nature.

[263]  R. Johns,et al.  eNOS expression is not altered in pulmonary vascular remodeling due to increased pulmonary blood flow. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[264]  Lieve Moons,et al.  Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele , 1996, Nature.

[265]  J. Sixma,et al.  The Origin of P-selectin as a Circulating Plasma Protein , 1997, Thrombosis and Haemostasis.

[266]  J. Hamilton,et al.  Stimulation of PAI-1 expression in endothelial cells by cultured vascular smooth muscle cells. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[267]  C W Turck,et al.  Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes. , 1994, Biochemistry.

[268]  M. D'Andrea,et al.  Increased Expression of Protease Activated Receptor-2 (PAR-2) in Balloon-Injured Rat Carotid Artery , 1999, Thrombosis and Haemostasis.

[269]  D. Ginsburg,et al.  Fatal haemorrhage and incomplete block to embryogenesis in mice lacking coagulation factor V , 1996, Nature.

[270]  S. Coughlin,et al.  Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. , 1994, The American journal of pathology.

[271]  S. Mousa,et al.  Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia and lumen stenosis following deep coronary arterial stent injury: evidence for the functional importance of integrin alpha v beta 3 and osteopontin expression during neointima formation. , 1997, Cardiovascular research.

[272]  T. Rabelink,et al.  Progressive vascular damage in hypertension is associated with increased levels of circulating P‐selectin , 1998, Journal of hypertension.

[273]  M. Runge,et al.  β3 Integrins Are Upregulated After Vascular Injury and Modulate Thrombospondin- and Thrombin-Induced Proliferation of Cultured Smooth Muscle Cells , 1998 .

[274]  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.

[275]  M. Ishikawa,et al.  Endothelium‐dependent inhibition of platelet aggregation , 1986, British journal of pharmacology.

[276]  P. Harrison,et al.  The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the ‘termination’ codon, TGA. , 1986, The EMBO journal.

[277]  P. Needleman,et al.  Sulfhydryl requirement for relaxation of vascular smooth muscle. , 1973, The Journal of pharmacology and experimental therapeutics.

[278]  Tae-Hee Lee,et al.  Prothrombin Kringle-2 Domain Has a Growth Inhibitory Activity against Basic Fibroblast Growth Factor-stimulated Capillary Endothelial Cells* , 1998, The Journal of Biological Chemistry.

[279]  J. Loscalzo,et al.  Unique antiplatelet effects of a novel S-nitrosoderivative of a recombinant fragment of von Willebrand factor, AR545C: in vitro and ex vivo inhibition of platelet function. , 1999, Blood.

[280]  J. Hoxie,et al.  Differential expression of functional protease-activated receptor-2 (PAR-2) in human vascular smooth muscle cells. , 1998, Arteriosclerosis, Thrombosis and Vascular Biology.

[281]  T. Barbui,et al.  Different Prevalence of Thromboembolism in the Subtypes of Congenital Antithrombin III Deficiency:Review of 404 Cases , 1987, Thrombosis and Haemostasis.

[282]  R. Silverstein,et al.  von Willebrand factor mediates platelet adhesion to virally infected endothelial cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[283]  Jean-PierreCazenave,et al.  Thrombin Receptor-Mediated Increase of Two Matrix Metalloproteinases, MMP-1 and MMP-3, in Human Endothelial Cells , 1997 .

[284]  S. M. Baker,et al.  Characterization of Protease-activated Receptor-2 Immunoreactivity in Normal Human Tissues , 1998, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[285]  Kenichi Watanabe,et al.  Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency , 1998, Annals of nuclear medicine.

[286]  J. Stamler,et al.  Biochemistry of nitric oxide and its redox-activated forms. , 1992, Science.

[287]  P. Hadváry,et al.  Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors. , 1994, The Journal of clinical investigation.

[288]  K. Shim,et al.  Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.