Article
Hematology
Aleksandr Shamanaev, Maxim Litvak, Ivan Ivanov, Priyanka Srivastava, Mao-Fu Sun, S. Kent Dickeson, Sunil Kumar, Tracey Z. Z. He, David Gailani
Summary: FXII plays a crucial role in the pathogenesis of diseases such as hereditary angioedema and surface-triggered thrombosis. Its activation and activity are enhanced when it binds to a surface. Recent studies on the structure and enzymology of FXII provide insights into its relationship with pathology and potential therapeutic targets for thrombo-inflammatory disorders.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2023)
Article
Allergy
Alona A. Merkulova, Sarah Abdalian, Sadiq Silbak, Alessandro Pinheiro, Alvin H. Schmaier
Summary: This study found that the activation of prekallikrein and cleavage of high-molecular-weight kininogen on human microvascular endothelial cells were regulated by the ambient concentration of C1 inhibitor and prolylcarboxypeptidase. These findings are important for understanding the function of endothelial cells and related diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bertrand Favier, Dominique J. Bicout, Remi Baroso, Marie-Helene Paclet, Christian Drouet
Summary: This study investigated the activation kinetics of the human kallikrein-kinin system (KKS) in vitro, showing that FXIIa and PKa are five times less active on ice than at 37 degrees C. The progress curve analysis of the in vitro KKS reconstitutions differed from a Michaelis-Menten mathematical simulation by a faster initial rate and a slower late rate.
BIOSCIENCE REPORTS
(2022)
Article
Hematology
Aleksandr Shamanaev, Maxim Litvak, Qiufang Cheng, Michal Ponczek, S. Kent Dickeson, Stephanie A. Smith, James H. Morrissey, David Gailani
Summary: The aim of this study was to identify the amino acids in the FXII EGF1 domain that are required for polyphosphate-dependent FXII functions. The results showed that Lys73, Lys74, Lys76, and Lys81 form a binding site for polyanionic substances, such as polyphosphate, which is crucial for surface-dependent FXII function.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Hematology
S. Kent Dickeson, Sunil Kumar, Mao-Fu Sun, Bassem M. Mohammed, Dennis R. Phillips, James C. Whisstock, Adam J. Quek, Edward P. Feener, Ruby H. P. Law, David Gailani
Summary: Patients with hereditary angioedema (HAE) experience episodes of bradykinin-induced swelling. A substitution of Lys(311) with glutamic acid in plasminogen (Plg) leads to increased bradykinin generation, indicating the pathogenic role of Glu(311) in HAE. The Glu(311) substitution introduces a lysine-binding site in the Plg kringle 3 domain, possibly altering the binding to kininogens.
Review
Immunology
Zivile Bekassy, Ingrid Lopatko Fagerstrom, Michael Bader, Diana Karpman
Summary: This review explores the complex interactions between the renin-angiotensin system, complement system, and kallikrein-kinin system, as well as their dysregulation in different conditions and therapeutic implications. Various mediators modulate the balance between vascular tone, inflammation, coagulation, and thrombosis during severe inflammatory and infectious diseases. These systems play important roles in cell biological functions, such as regulating vascular tone, inflammation, and thrombosis.
NATURE REVIEWS IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Michal B. Ponczek
Summary: Kininogens are multidomain glycoproteins with important roles in the intrinsic pathway of coagulation and the generation of the vasoactive peptide bradykinin. Despite previous failures to crystallize kininogen, new advancements in cryo-electron microscopy offer opportunities to study its structure at an atomic level.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Mahmoud E. Youssef, Mustafa A. Abdel-Reheim, Mohamed A. Morsy, Mahmoud El-Daly, Gamal M. K. Atwa, Galal Yahya, Simona Cavalu, Sameh Saber, Ahmed Gaafar Ahmed Gaafar
Summary: This study examined the effectiveness of the antithrombotic agent dabigatran in treating arthritis in rats. The results showed that dabigatran had anti-inflammatory and antioxidant effects, making it a potential novel therapeutic strategy for arthritis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Alessandro de Sa Pinheiro, James W. Kazura, Ana Acacia Pinheiro, Alvin H. Schmaier
Summary: Malaria is a parasitic disease that is globally significant, especially in endemic regions, and is a major cause of death in children. The mechanisms of cerebral malaria, particularly the role of bradykinin, are not fully understood, but recent discoveries suggest its potential involvement in the disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Medicine, General & Internal
Ana Carolina Oliveira, Amanda Roberta Revoredo Vicentino, Daniele Andrade, Isabela Resende Pereira, Leonardo Saboia-Vahia, Otacilio da Cruz Moreira, Carla Eponina Carvalho-Pinto, Julia Barbalho da Mota, Leonardo Maciel, Glaucia Vilar-Pereira, Joao B. Pesquero, Joseli Lannes-Vieira, Pierre Sirois, Antonio Carlos Campos de Carvalho, Julio Scharfstein
Summary: We investigated the role of B1R receptor in the development of Chagas disease caused by Trypanosoma cruzi. Our findings suggest that blocking the B1R receptor can reduce heart parasitism and cardiac injury in acute and chronic Chagas disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Nicholas P. Giangreco, Guillaume Lebreton, Susan Restaino, Maryjane Farr, Emmanuel Zorn, Paolo C. Colombo, Jignesh Patel, Rajesh Kumar Soni, Pascal Leprince, Jon Kobashigawa, Nicholas P. Tatonetti, Barry M. Fine
Summary: This study utilized proteomics to identify potential biomarkers for predicting post-transplant survival in heart failure patients. The analysis identified six protein markers that have a predictive performance above AUROC of 0.6, including Prothrombin, anti-plasmin, Factor IX, carboxypeptidase 2, HGF activator, and low molecular weight kininogen. Additionally, the analysis revealed that upregulation of components of the kallikrein-kinin system and downregulation of kininogen prior to transplant were associated with improved survival after transplant.
SCIENTIFIC REPORTS
(2022)
Article
Biochemical Research Methods
Tanja Gangnus, Bjoern B. Burckhardt
Summary: The kallikrein-kinin system is involved in physiological and pathophysiological processes, but understanding of its in vivo role is limited. A sensitive LC-MS/MS platform has been developed to accurately determine kinin levels, successfully detecting low pg/mL levels in the plasma of healthy volunteers.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Review
Physiology
Guacyara Motta, Luiz Juliano, Jair Ribeiro Chagas
Summary: This review summarizes the history and evolution of human plasma kallikrein, and explores its role in cell biology and inflammatory processes. It also examines the development of natural plasma protein inhibitors.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Hematology
Zu-Lin Chen, Pradeep K. Singh, Katharina Horn, Marissa R. Calvano, Shigeru Kaneki, Keith R. McCrae, Sidney Strickland, Erin H. Norris
Summary: A dysregulated plasma contact system is involved in various pathological conditions. 3E8 anti-HK antibody blocks HK cleavage and bradykinin generation in human and mouse plasma, and inhibits contact system-induced bradykinin generation. It also inhibits the activation of factor XI, prekallikrein, and FXII, providing a novel strategy to treat contact system dysregulation-related diseases.
Article
Medicine, General & Internal
Anne Cathrine Godtfredsen, Jorgen Brodersen Gram, Stephanie Thuy Duong Pham, Britta Blume Dolleris, Jan Stener Jorgensen, Johannes Jakobsen Sidelmann, Yaseelan Palarasah
Summary: This study aimed to investigate the effect of preeclampsia on the contact system in blood. The researchers found that women with preeclampsia had significantly lower kallikrein generating capacity, prekallikrein, and cleaved H-kininogen compared to the controls. However, there were no significant differences in the concentration of coagulation factor XII, H-kininogen, and complement C1 esterase inhibitor between the two groups. These findings suggest that the contact system is affected in preeclampsia, potentially contributing to the pathophysiology of the disease.
FRONTIERS IN MEDICINE
(2022)
Editorial Material
Medicine, Research & Experimental
Alvin H. Schmaier
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Oncology
Hamza N. Gokozan, Judah D. Friedman, Alvin H. Schmaier, Katharine A. Downes, Lisa A. Farah, Hollie M. Reeves
CLINICAL LUNG CANCER
(2019)
Article
Hematology
Alvin H. Schmaier, Jonas Emsley, Edward P. Feener, David Gailani, Jose W. P. Govers-Riemslag, Allen P. Kaplan, Coen Maas, James H. Morrissey, Thomas Renne, Johannes J. Sidelmann, Joost C. M. Meijers
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2019)
Editorial Material
Hematology
Alvin H. Schmaier
Editorial Material
Cell Biology
Alvin H. Schmaier
Review
Biochemistry & Molecular Biology
Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A. S. Peres, Diogo B. Peruchetti, Carlos P. Gomes, Alvin H. Schmaier, Patricia R. M. Rocco, Ana Acacia S. Pinheiro, Celso Caruso-Neves
Summary: Since the outbreak of COVID-19, there has been a bidirectional interaction between kidney disease and the progression of the disease. Kidney disease is an independent risk factor for mortality in COVID-19 patients and can lead to acute kidney injury (AKI) and chronic kidney disease (CKD) in these patients. However, current clinical examinations may not detect kidney damage in COVID-19 patients until an advanced stage. Studies have identified the development of subclinical acute kidney injury (subAKI) syndrome in COVID-19 patients, characterized by significant tubule interstitial injury without changes in estimated glomerular filtration rate. Changes in the protein endocytosis machinery in proximal tubule epithelial cells (PTECs) have been proposed as a potential mechanism for the development of subAKI. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Critical Care Medicine
Jessica Traeger, Jason Makii, Thomas Ostergard, Robert Barcelona, Alvin Schmaier
CRITICAL CARE MEDICINE
(2019)
Review
Hematology
Alvin H. Schmaier, Evi X. Stavrou
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2019)
Article
Hematology
Alona Merkulova, Steven C. Mitchell, Evi X. Stavrou, Gabriel L. Forbes, Alvin H. Schmaier
Review
Surgery
Nikunj N. Trivedi, Steven J. Fitzgerald, Alvin H. Schmaier, Glenn D. Wera
Meeting Abstract
Allergy
Alvin H. Schmaier, Kenneth A. Bauer, Marco Cicardi, Jacques Hebert, Douglas T. Johnston, Paula J. Busse, Kim Paes, Daniel J. Sexton, Jon Kenniston, Christina Nurse, Rafael H. Zaragoza
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2019)
Meeting Abstract
Hematology
Michael A. Suster, Debnath Maji, Lalitha V. Nayak, Christina Jenkins, Susan Hunter, Alvin H. Schmaier, Pedram Mohseni, Sanjay Ahuja
Meeting Abstract
Hematology
Lalitha V. Nayak, Stephanie Lapping, Andrei Maiseyeu, Alvin H. Schmaier, Mukesh Jain
Meeting Abstract
Hematology
Dewen You, Suman Kundu, Alvin H. Schmaier, Alok A. Khorana, Keith R. McCrae
Meeting Abstract
Hematology
Jevgenia Zilberman-Rudenko, Stephanie E. Reitsma, Cristina Puy, Stephanie A. Smith, Chantal P. Wiesenekker, Erik I. Tucker, Richard J. Travers, Coen Maas, Rolf T. Urbanus, David Gailani, Alvin H. Schmaier, Florea Lupu, James H. Morrissey, Andras Gruber, Owen J. McCarty
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2018)