Affiliation: Case Western Reserve University
- The elusive physiologic role of Factor XIIAlvin H Schmaier
Division of Hematology and Oncology, Case Western Reserve University, Cleveland, Ohio 44106 7284, USA
J Clin Invest 118:3006-9. 2008..This study describes a novel biologic surface for FXII activation and activity, which initiates inflammatory events independent of hemostasis...
- The physiologic basis of assembly and activation of the plasma kallikrein/kinin systemAlvin H Schmaier
Thromb Haemost 91:1-3. 2004
- Mapping the interaction between high molecular mass kininogen and the urokinase plasminogen activator receptorFakhri Mahdi
Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 279:16621-8. 2004..Therefore, HK interacts with suPAR at several sites. HK binds to uPAR as part of its interaction with its multiprotein receptor complex on HUVEC, and the biological functions that depend upon this binding are modulated by urokinase...
- The plasma kallikrein/kinin and renin angiotensin systems in blood pressure regulation in sepsisZia Shariat-Madar
Department of Internal Medicine, The University of Michigan, Ann Arbor, Michigan 48109-0640, USA
J Endotoxin Res 10:3-13. 2004..Understanding the interactions between these two systems may lead to development of better pharmacological treatments for endotoxin-induced shock...
- Mapping the interaction of bradykinin 1-5 with the exodomain of human protease activated receptor 4Marvin T Nieman
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
FEBS Lett 579:25-9. 2005..The N-terminal arginine on RPPGF binds to the P2 position or proline46 on PAR4 to block thrombin cleavage. These data indicate that RPPGF influences thrombin activity by binding to the thrombin cleavage site on both PAR4 and PAR1...
- Are maternal antiplatelet antibodies a prothrombotic condition leading to miscarriage?Alvin H Schmaier
Case Western Reserve University, Cleveland, Ohio, USA
J Clin Invest 121:4241-3. 2011..have identified a potential reason for this - they find that in the majority of pregnant mice, anti-GPIbα antibodies enhance platelet activation and accelerate thrombus formation in the placenta and that this leads to miscarriage...
- The plasma kallikrein-kinin system: its evolution from contact activationA H Schmaier
Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, 10900 Euclid Avenue, Cleveland, OH 44106, USA
J Thromb Haemost 5:2323-9. 2007..The present characterizations of this system, which incorrectly had been thought to initiate coagulation, represent an evolution of understanding in this field...
- Assembly, activation, and physiologic influence of the plasma kallikrein/kinin systemAlvin H Schmaier
Department of Medicine, Case Western Reserve University, University Hospital Case Medical Center, Division of Hematology and Oncology, Cleveland, OH 44106 7284, United States
Int Immunopharmacol 8:161-5. 2008..Better understanding of this system may lead to insight into mechanisms for arterial thrombosis, independent of hemostasis...
- Factor XII: new life for an old proteinA H Schmaier
Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio 44106 7284, USA
Thromb Haemost 104:915-8. 2010..These studies indicate that XII stimulates angiogenesis, a physiologic function independent of contact activation...
- Interaction of thrombin with PAR1 and PAR4 at the thrombin cleavage siteMarvin T Nieman
Division of Hematology Oncology, Case Western Reserve University, Cleveland, Ohio 44106 7284, USA
Biochemistry 46:8603-10. 2007..It also implies that factors other than the hirudin-like binding region on PAR1 exodomain predominate in influencing PAR1 cleavage on cells...
- Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosisEvi Stavrou
Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, OH 44106 7284, USA
Thromb Res 125:210-5. 2010..These combined studies suggest that FXII may become a pharmacologic target to reduce arterial thrombosis risk and promote cell repair after injury, without influencing hemostasis...
- Plasma prekallikrein: a risk marker for hypertension and nephropathy in type 1 diabetesAyad A Jaffa
Department of Medicine, Endocrinology Diabetes Medical Genetics, Medical University of South Carolina, 114 Doughty Street, PO Box 250776, Charleston, SC 29425, USA
Diabetes 52:1215-21. 2003....
- Assembly and activation of the plasma kallikrein/kinin system: a new interpretationZia Shariat-Madar
Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
Int Immunopharmacol 2:1841-9. 2002..Insights into the integrated role of these two systems may afford the development of novel therapeutic drugs to manage hypertension and thrombosis...
- Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesisGretchen A LaRusch
Division of Hematology and Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
Blood 115:5111-20. 2010..In sum, FXII initiates signaling mediated by uPAR, beta(1) integrin, and the EGFR to induce human umbilical vein endothelial cell proliferation, growth, and angiogenesis...
- Recombinant prolylcarboxypeptidase activates plasma prekallikreinZia Shariat-Madar
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, 5301 MSRB III, 1150 W Medical Center Drive, Ann Arbor, MI 48109 0649, USA
Blood 103:4554-61. 2004..These investigations indicate that rPRCP is functionally identical to isolated HUVEC PRCP and is a major HUVEC membrane-expressed, PK-activating enzyme detected in the intravascular compartment...
- AbetaPP/APLP2 family of Kunitz serine proteinase inhibitors regulate cerebral thrombosisFeng Xu
Department of Medicine, Stony Brook University, Stony Brook, New York 11794 8153, USA
J Neurosci 29:5666-70. 2009..Together, these results indicate that AbetaPP and APLP2 share overlapping anticoagulant functions with regard to regulating thrombosis after cerebral vascular injury...
- Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activatorZia Shariat-Madar
Division of Hematology and Oncology, Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, Michigan 48109 0640, USA
J Biol Chem 277:17962-9. 2002..The K(m) of PK activation by PRCP is 6.7 nm. PRCP antigen is present on the membrane of fixed but not permeabilized HUVEC. PRCP appears to be a HUVEC-associated PK activator...
- Complications from vascular disrupting agents and angiogenesis inhibitors: aberrant control of hemostasis and thrombosisWillem J van Heeckeren
Case Comprehensive Cancer Center, Case School of Medicine, Division of Hematology Oncology, University Hospitals Case Medical Center, Cleveland, Ohio 44106, USA
Curr Opin Hematol 14:468-80. 2007..To discuss thrombotic and hemorrhagic complications from angiogenesis inhibitors and vascular disrupting agents, pathogenesis, and recommendations for prophylaxis and management of those complications...
- Thrombotic microangiopathy in haematopoietic stem cell transplantation: diagnosis and treatmentCecilia M Choi
Department of Medicine, Division of Hematology Oncology, University Hospitals Case Medical Center, Cleveland, Ohio, USA
Drugs 69:183-98. 2009..One candidate may be daclizumab, especially in those with mild to moderate TMA. Rituximab therapy or the addition of defibrotide may also be beneficial. In general, plasma exchange is not recommended...
- Deletion of murine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosisSergei Merkulov
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Blood 111:1274-81. 2008..These results suggest that a single gene, mKng1, is responsible for production of plasma kininogen, and that plasma HK contributes to induced arterial thrombosis in mice...
- Myeloperoxidase interacts with endothelial cell-surface cytokeratin 1 and modulates bradykinin production by the plasma Kallikrein-Kinin systemJoshua M Astern
Burnett Womack, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7155, USA
Am J Pathol 171:349-60. 2007..This study identifies CK1 as a facilitator of MPO-mediated vascular responses and thus provides a new paradigm by which MPO affects vasoregulatory systems...
- Synthesis of novel peptide inhibitors of thrombin-induced platelet activationFernanda M Burke
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA
Chem Biol Drug Des 68:235-8. 2006....
- The preparation and characterization of novel peptide antagonists to thrombin and factor VIIa and activation of protease-activated receptor 1Marvin T Nieman
Thromgen Inc, Ann Arbor, MI 48109-0640, USA
J Pharmacol Exp Ther 311:492-501. 2004..TH146 and MAP4-TH146 inhibit human and mouse platelet aggregation and mouse thrombosis. Analogs of RPPGF are model compounds to develop PAR1 activation antagonists as well as direct inhibitors to thrombin and factor VIIa...
- A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell linesChristopher H Chay
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0946, USA
Urology 60:760-5. 2002..CONCLUSIONS: These data indicate that a functional PAR1 is expressed on prostate cancer cell lines. The prostate cancer cell lines expressing PAR1 appear to have an association with increased bone metastases...
- Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expressionYelena Krijanovski
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109 0640, USA
Blood 101:4430-6. 2003..Fitzgerald DNA has a normal exon 10, but a 17-bp mutation in intron 9. These combined results indicate that mutations in the kininogen gene may differentially affect biosynthesis, processing, and/or secretion of HK...
- Mechanisms of Arg-Pro-Pro-Gly-Phe inhibition of thrombinAhmed A K Hasan
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0640, USA
Am J Physiol Heart Circ Physiol 285:H183-93. 2003..These studies indicate that RPPGF is a bifunctional inhibitor of thrombin: it binds to PAR1 to prevent thrombin cleavage at Arg41 and interacts with the active site of alpha-thrombin...
- The relative priority of prekallikrein and factors XI/XIa assembly on cultured endothelial cellsFakhri Mahdi
Department of Internal Medicine, Hematology and Oncology Division, The University of Michigan, Ann Arbor, Michigan 48109 0640, USA
J Biol Chem 278:43983-90. 2003..PK preferential binding to endothelial cells contributes to their anticoagulant nature...
- Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranesFakhri Mahdi
Department of Internal Medicine and Pathology, University of Michigan, Ann Arbor, MI 48109-0640, USA
Blood 99:3585-96. 2002..Thus, physiologic FXII expression on HUVECs is secondary to HK binding and highly restricted in its ability to initiate prekallikrein or FXI activation...
- The plasma kallikrein-kinin system counterbalances the renin-angiotensin systemAlvin H Schmaier
University of Michigan, Departments of Internal Medicine and Pathology, 5301 Medical Science Research Building III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0640, USA
J Clin Invest 109:1007-9. 2002
- Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsisInes J Laudes
Departments of Pathology and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan
Am J Pathol 160:1867-75. 2002..Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a...
- Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activatorClaudia R Moreira
Departmento de Bioquimica, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
FEBS Lett 523:167-70. 2002..On immunoblot, prolylcarboxypeptidase antigen is associated with HUVEC matrix. These studies indicate that prolylcarboxypeptidase is the matrix PK activator...
- Thrombostatin, a bradykinin metabolite, reduces platelet activation in a model of arterial wall injuryAlejandro R Prieto
Department of Internal Medicine, Division of Cardiology, Michigan State University, East Lansing, MI 48824, USA
Cardiovasc Res 53:984-92. 2002..5x (P<0.03) using laser-light scattering and platelet adhesion by 1.8x (P<0.02). CONCLUSION: Thrombostatin or aspirin independently decreases evidence of platelet activation in the canine carotid artery model of BA injury...
- Factor VLeiden inhibits fibrinolysis in vivoAndrew C Parker
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109 0644, USA
Circulation 110:3594-8. 2004..Factor V(Leiden) (fV(Leiden)) predisposes to thrombosis by enhancing thrombin formation. This study tested the hypothesis that fV(Leiden) inhibits fibrinolysis in vivo...
- The kallikrein-kinin and the renin-angiotensin systems have a multilayered interactionAlvin H Schmaier
The Univ of Michigan, 5301 MSRB III, 1150 West Medical Center Dr, Ann Arbor, MI 48109 0640, USA
Am J Physiol Regul Integr Comp Physiol 285:R1-13. 2003..This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions...
- Detection of amide I signals of interfacial proteins in situ using SFGJie Wang
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
J Am Chem Soc 125:9914-5. 2003..Our studies indicate that different proteins generate different SFG amide signals at the polystyrene/protein solution interface, showing that they have different interfacial coverage, secondary structure, or orientation...
- Ordered adsorption of coagulation factor XII on negatively charged polymer surfaces probed by sum frequency generation vibrational spectroscopyXiaoyun Chen
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Anal Bioanal Chem 388:65-72. 2007..These investigations indicate that negatively charged surfaces facilitate or induce FXII autoactivation on the molecular level by imposing specific orientation and ordering on the adsorbed protein molecules...
- Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclinZia Shariat-Madar
Hematology Oncology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
Blood 108:192-9. 2006..These investigations indicate a pathway for thrombosis risk reduction via the plasma kallikrein/kinin and renin angiotensin systems...
- Platelet aggregation testing in platelet-rich plasma: description of procedures with the aim to develop standards in the fieldLan Zhou
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0640, USA
Am J Clin Pathol 123:172-83. 2005..Our intent is to stimulate interest in the development of professional guidelines for platelet function testing in the clinical laboratory...
- Heparan sulfate modulates kinin release by Trypanosoma cruzi through the activity of cruzipainAna Paula C A Lima
Instituto de Biofisica Carlos Chagas Filho, Universidade do Brasil, CCS, Bloco G, , CEP 21944-900, Rio de Janeiro, Brazil
J Biol Chem 277:5875-81. 2002..These studies suggest that the efficiency of T. cruzi to initiate kinin release is potently enhanced by the mutual interactions between cruzipain, HK, and heparan sulfate proteoglycans...
- REGULATION OF KININ DELIVERY ON HUVECAlvin H Schmaier; Fiscal Year: 2010..The proposal aims to characterize the first recognized prothrombotic mouse due to increased reactive oxygen therapy. Studies will also examine if the prothrombotic and hypertensive mechanisms are linked. ..
- REGULATION OF KININ DELIVERY ON HUVECAlvin Schmaier; Fiscal Year: 2007..These investigations will lead to the recognition of new targets for drug development that could be used to treat hypertension and decrease thrombosis risk. ..
- Thrombostatin-A Thrombin Receptor InhibitorAlvin Schmaier; Fiscal Year: 2006..Second, the preparation of an IND application for its human use for one indication will be achieved. Thrombostatin(tm) has the opportunity to be a first-in-its-class thrombin receptor activation antagonist. ..
- REGULATION OF KININ DELIVERY ON HUVECAlvin Schmaier; Fiscal Year: 2004..These studies are intended to characterize this system's contribution to vascular biology and to develop new strategies to modulate intravascular thrombosis. ..
- PLASMA PROTEIN PHENOTYPING OF PROTHROMBOTIC MICEAlvin Schmaier; Fiscal Year: 2003..These studies could serve as a basis for the development of a global assay(s) to predict the prothrombotic state in man. (End of Abstract.) ..
- REGULATION OF KININ DELIVERY ON HUVECAlvin Schmaier; Fiscal Year: 2000..Modulation of bradykinin liberation is important in the regulation of local blood pressure in coronary, renal, pulmonary, and cerebral circulations. ..