Annexin A4 inhibits sulfatide‐induced activation of coagulation factor XII

2020 ◽  
Vol 18 (6) ◽  
pp. 1357-1369 ◽  
Author(s):  
Moeka Nakayama ◽  
Hitomi Miyagawa ◽  
Yumiko Kuranami ◽  
Miyuki Tsunooka‐Ota ◽  
Yoshiki Yamaguchi ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor Xii ◽  
Annexin A4

scholarly journals Diagnosis of hereditary Angioedema by genetic mutation of coagulation factor XII

2021 ◽  
Vol 147 (2) ◽  
pp. AB23
Author(s):  
Natasha Ferraroni ◽  
Gabriela Yoshimoto ◽  
Camila Veronez ◽  
Luiza Silva ◽  
Marina Batista ◽  
...  
Keyword(s):  
Hereditary Angioedema ◽  
Coagulation Factor ◽  
Genetic Mutation ◽  
Factor Xii

Fibrinolyse- und Thrombophilieparameter unter systemischer Prostaglandin E1-Therapie bei peripherer arterieller Verschlusskrankheit

VASA ◽  
2003 ◽  
Vol 32 (3) ◽  
pp. 145-148 ◽  
Author(s):  
Kuss ◽  
Heidrich ◽  
Koettgen
Keyword(s):  
Coagulation Factor ◽  
Plasminogen Activator Inhibitor ◽  
Bleeding Risk ◽  
Arterial Disease ◽  
Prostaglandin E ◽  
Factor Xii ◽  
Significant Difference ◽  
Peripheral Arterial ◽  
Fibrinolytic Capacity

Background: The study was designed to evaluate if there is any evidence of a hyperfibrinolytic bleeding-risk under systemic treatment with prostaglandin E1 (PGE1) of patients with peripheral arterial disease (PAD). Patients and methods: The in vivo effect of PGE1 on the fibrinolytic and hemostatic process was tested on 15 patients before and after treatment with Alprostadil for 21 days using D-dimers (DD), fibrinogen, prothrombin time (PT), partial thromboplastin time (PTT), antithrombin (AT), ProC-Global®, plasminogen, plasminogen activator inhibitor activity (PAI), alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity (fib. cap.). Results: There was no significant difference in DD, fibrinogen, PT, PTT, AT, ProC-Global®, plasminogen, PAI, alpha2-antiplasmin, coagulation factor XII, basal and activated fibrinolytic capacity observed after the treatment. Conclusion: Summarizing this study there is no hyperfibrinolytic bleeding-risk after the systemic therapy with Alprostadil to be expected.

Targeted deletion of murine coagulation factor XII gene-a model for contact phase activation in vivo

2004 ◽  
Vol 92 (09) ◽  
pp. 503-508 ◽  
Author(s):  
Hans-Ulrich Pauer ◽  
Thomas Renné ◽  
Bernhard Hemmerlein ◽  
Tobias Legler ◽  
Saskia Fritzlar ◽  
...  
Keyword(s):  
Fetal Loss ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Mendelian Inheritance ◽  
Biological Role ◽  
Factor Xii ◽  
Wild Type ◽  
Contact Phase ◽  
Health And Disease

SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII-/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII-/- mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore, matings of FXII-/- males and FXII-/females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII-/females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII-/mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII-/mice will be helpful to elucidate the biological role(s) of FXII in health and disease.

Structure of plasma and tissue kallikreins

2013 ◽  
Vol 110 (09) ◽  
pp. 423-433 ◽  
Author(s):  
Monika Pathak ◽  
Szu Shen Wong ◽  
Ingrid Dreveny ◽  
Jonas Emsley
Keyword(s):  
Molecular Weight ◽  
Serine Proteases ◽  
Molecular Mechanisms ◽  
Substrate Recognition ◽  
Coagulation Factor ◽  
Structural Data ◽  
Pressure Control ◽  
Factor Xii ◽  
Zymogen Activation ◽  
Kinin System

SummaryThe kallikrein kinin system (KKS) consists of serine proteases involved in the production of peptides called kinins, principally bradykinin and Lys-bradykinin (kallidin). The KKS contributes to a variety of physiological processes including inflammation, blood pressure control and coagulation. Here we review the protein structural data available for these serine proteases and examine the molecular mechanisms of zymogen activation and substrate recognition focusing on plasma kallikrein (PK) and tissue kallikrein (KLK1) cleavage of kininogens. PK circulates as a zymogen bound to high-molecular-weight kininogen (HK). PK is activated by coagulation factor XIIa and then cleaves HK to generate bradykinin and factor XII to generate further XIIa. A structure has been described for the activated PK protease domain in complex with the inhibitor benzamidine. Kallikrein-related peptidases (KLKs) have a distinct domain structure and exist as a family of 15 genes which are differentially expressed in many tissues and the central nervous system. They cleave a wide variety of substrates including low-molecular-weight kininogen (LK) and matrix proteins. Crystal structures are available for KLK1, 3, 4, 5, 6 and 7 activated protease domains typically in complex with S1 pocket inhibitors. A substrate mimetic complex is described for KLK3 which provides insight into substrate recognition. A zymogen crystal structure determined for KLK6 reveals a closed S1 pocket and a novel mechanism of zymogen activation. Overall these structures have proved highly informative in understanding the molecular mechanisms of the KKS and provide templates to design inhibitors for treatment of a variety of diseases.

scholarly journals Cold-induced urticarial autoinflammatory syndrome related to factor XII activation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jörg Scheffel ◽  
Niklas A. Mahnke ◽  
Zonne L. M. Hofman ◽  
Steven de Maat ◽  
Jim Wu ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Gene Mutations ◽  
Coagulation Factor ◽  
Hek293 Cells ◽  
Receptor Protein ◽  
Local Source ◽  
Factor Xii ◽  
Mutant Proteins ◽  
Hereditary Autoinflammatory Diseases ◽  
Immune Pathway

AbstractHereditary autoinflammatory diseases are caused by gene mutations of the innate immune pathway, e.g. nucleotide receptor protein 3 (NLRP3). Here, we report a four-generation family with cold-induced urticarial rash, arthralgia, chills, headache and malaise associated with an autosomal-dominant inheritance. Genetic studies identify a substitution mutation in gene F12 (T859A, resulting in p.W268R) which encodes coagulation factor XII (FXII). Functional analysis reveals enhanced autocatalytic cleavage of the mutated protein and spontaneous FXII activation in patient plasma and in supernatant of transfected HEK293 cells expressing recombinant W268R-mutated proteins. Furthermore, we observe reduced plasma prekallikrein, cleaved high molecular weight kininogen and elevated plasma bradykinin. Neutrophils are identified as a local source of FXII. Interleukin-1β (IL-1β) is upregulated in lesional skin and mononuclear donor cells exposed to recombinant mutant proteins. Treatment with icatibant (bradykinin-B2-antagonist) or anakinra (interleukin-1-antagonist) reduces disease activity in patients. In conclusion, our findings provide a link between contact system activation and cytokine-mediated inflammation.

scholarly journals Coagulation Factor XII protects neurons from apoptosis by triggering a crosstalk between HGFR/c-Met and EGFR/ErbB1 signaling pathways

2020 ◽  
Author(s):  
Eugénie Garnier ◽  
Damien Levard ◽  
Carine Ali ◽  
Yannick Hommet ◽  
Tiziana Crepaldi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Neuronal Cell ◽  
Coagulation Factor ◽  
Receptor Activation ◽  
Target Cells ◽  
Cultured Neurons ◽  
Factor Xii ◽  
Protective Effects

Abstract Background Factor XII (FXII) is a serine protease that participates in the intrinsic coagulation pathway. Several studies have shown that plasmatic FXII exert a deleterious role in cerebral ischemia and traumatic brain injury by promoting thrombo-inflammation. Nevertheless, the direct impact of FXII on neuronal cell fate remains unknown.Methods We investigated whether FXII influenced neuronal death induced in vivo by stereotaxic injection of N-methyl-D-Aspartate (NMDA) and in vitro by serum deprivation of cultured neurons.Results We found that FXII reduced brain lesions induced in vivo and protected cultured neurons from apoptosis through a growth factor-like effect. This mechanism was triggered by direct interaction with epidermal growth factor (EGF) receptor, activation of this receptor and engagement of anti-apoptotic intracellular pathways. Interestingly, the “proteolytically” active and two-chain form of FXII, αFXIIa, exerted additional protective effects by converting the pro-form of hepatocyte growth factor (HGF) into its mature form, which in turn activated HGF receptor (HGFR/c-Met) pathway. Lastly, the use of non-proteolytic FXII (αFXIIa-PPACK) unveiled an alternative EGFR and HGFR co-activation pathway, through co-receptor transphosphorylation. Conclusion This study describes novel mechanisms of action of FXII and discloses neurons as target cells for the protective effects of single and double-chain forms of FXII.

Sign in / Sign up

Export Citation Format

Share Document