Participation of Hageman Factor Dependent Pathways in Human Disease States

1977 ◽  
Vol 38 (04) ◽  
pp. 0751-0775 ◽  
Author(s):  
Robert W. Colman ◽  
Patrick Y. Wong
Keyword(s):  
Human Disease ◽  
Gouty Arthritis ◽  
Factor Xii ◽  
Hageman Factor ◽  
Disease States ◽  
Artery Disease ◽  
Extracorporeal Bypass ◽  
Allergic Disorders

SummaryAbnormalities of Hageman factor dependent pathways have been described in a wide variety of human disease states. Congenital deficiencies of factor XII (Hageman trait) prekallikrein (Fletcher trait) and high molecular weight kininogen (Williams, Fitzgerald and Flaujeac traits) although resulting in profound in vitro changes, do not cause in vivo difficulties. In contrast, deficiency of Cl esterase inhibitor (hereditary angioedema) results in significant morbidity and mortality. Acquired diseases may exhibit decreased synthesis of these three proteins in cirrhosis and dengue fever. In vivo activation of factor XII initiated pathways occur in septic shock, disseminated or localized intravascular coagulation, typhoid fever, polycythemia vera, hyperbetalipoproteinemia, coronary artery disease, nephrotic syndrome, transfusion reactions, hemodialysis and extracorporeal bypass. Activation of both the intrinsic system and tissue mediators contribute to the vasomotor phenomena in carcinoid syndrome and postgastrectomy dumping. Roles for factor XII, prekallikrein and kininogen have been suggested in gouty arthritis, allergic disorders and cystic fibrosis but the evidence is not yet convincing in these disorders.

In vivo activation and functions of the protease factor XII

2014 ◽  
Vol 112 (11) ◽  
pp. 868-875 ◽  
Author(s):  
Jenny Björkqvist ◽  
Katrin Nickel ◽  
Evi Stavrou ◽  
Thomas Renné
Keyword(s):  
Cardiovascular System ◽  
Inflammatory Diseases ◽  
Contact System ◽  
Factor Xii ◽  
Hageman Factor ◽  
Current Review ◽  
Exciting Opportunity ◽  
System Factor

SummaryCombinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. The current review concentrates on activators and functions of the FXII-driven contact system in vivo. Elucidating its physiologic activities offers the exciting opportunity to develop strategies for the safe interference with both thrombotic and inflammatory diseases.

scholarly journals Coagulation factor XII in thrombosis and inflammation

Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1903-1909 ◽  
Author(s):  
Coen Maas ◽  
Thomas Renné
Keyword(s):  
Thrombus Formation ◽  
Coagulation Factor ◽  
Contact System ◽  
Inflammatory Disorder ◽  
Factor Xii ◽  
Kinin System ◽  
Disease States ◽  
Exciting Opportunity

Abstract Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII–driven contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate, provides protection from thromboembolic diseases without interfering with hemostasis. This suggests that the polyphosphate/factor XII axis contributes to thrombus formation while being dispensable for hemostatic processes. In contrast to deficiency in factor XII providing safe thromboprotection, excessive FXII activity is associated with the life-threatening inflammatory disorder hereditary angioedema. The current review summarizes recent findings of the polyphosphate/factor XII–driven contact system at the intersection of procoagulant and proinflammatory disease states. Elucidating the contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory disorders.

Detection of Activation of the Contact System of Coagulation In Vitro and In Vivo: Quantitation of Activated Hageman Factor-C1-Inhibitor and Kallikrein-C1-Inhibitor Complexes by Specific Radioimmunoassays

1987 ◽  
Vol 58 (02) ◽  
pp. 778-785 ◽  
Author(s):  
J H Nuijens ◽  
C C M Huijbregts ◽  
M Cohen ◽  
G O Navis ◽  
A de Vries ◽  
...  
Keyword(s):  
Contact System ◽  
Factor Xii ◽  
Plasma Samples ◽  
C1 Inhibitor ◽  
Hageman Factor ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Kallikrein Activity

SummaryRadioimmunoassays (RIAs) for the detection of C1-inhihitor (C1-Inh) complexed to either kallikrein or activated Hageman factor (factor XIIa) are described. Kallikrein-C1-Inh or factor XIIa-C1-Inh complexes were bound to Scpharosc to which monospecific antibodies against (pre)kallikrein or factor XII, respectively, were coupled. Bound complexes were subsequently detected by an incubation with affinity purified 125I-labeled antibodies against Ci-Inh. These RIAs were used to detect activation of the contact system of coagulation in vitro and in vivo. Addition of dextran sulfate (DXS) (20 μg/ml) to fresh plasma resulted at 37° C in the rapid generation of amidolytic kallikrein activity, which was maximal after 1 to 2 min of incubation and subsequently decreased within a few minutes. The generation of kallikrein activity coincided with the appearance of both kallikrein-C1-Inh and factor XIIa-C1-Inh complexes. However, in contrast to kallikrein activity, both types of complexes remained detectable in the incubation mixtures during the incubation period. Experiments with purified kallikrein, C1-Inh and partly purified β-factor XIIa, and activation experiments in plasmas deficient in either factor XII or prekallikrein, demonstrated the specificity of both RIAs. The minimal amount of DXS that resulted in the generation of measurable amounts of both types of complexes in plasma was 2-3 μg per ml. Similar experiments with kaolin showed that with limiting amounts of activator (1-2 mg/ ml), only kallikrein-C1-Inh complexes were detected in plasma. When larger amounts of kaolin were added to plasma, factor XIIa-C1-Inh complexes were additionally detected in plasma. In plasma samples obtained from healthy donors under conditions that prevented activation of the contact system in vitro, very low levels of both factor XIIa-C1-Inh and kallikrein-C1-Inh complexes were measured, representing approximately 0.3% activation of both factor XII and prekallikrein. In serial plasma samples from a patient with adult respiratory distress syndrome, increased levels of both types of complexes were detected. The radioimmunoassays described in this paper provide useful tools to detect activation of the contact system in vitroas well as in vivo.

Bmk9 and Uricase Nanoparticle Complex for the Treatment of Gouty Arthritis and Uric Acid Nephropathy

2021 ◽  
Vol 17 (10) ◽  
pp. 2071-2084
Author(s):  
Tianjiao Han ◽  
Meiying Wang ◽  
Wenchao Li ◽  
Mingxing An ◽  
Hongzheng Fu
Keyword(s):  
Uric Acid ◽  
Drug Loading ◽  
Gouty Arthritis ◽  
The Body ◽  
Key Points ◽  
Uric Acid Nephropathy ◽  
Charged Carrier ◽  
Dual Drug

Uric acid is the final product of purine metabolism, and excessive serum uric acid can cause gouty arthritis and uric acid nephropathy. Therefore, lowering the uric acid level and alleviating inflammation in the body are the key points to treating these diseases. A stable nanosuspension of peptide BmK9 was prepared by the precipitation-ultrasonication method. By combining uricase on the surface of a positively charged carrier, a complex consisting of neutral rod-shaped BmK9 and uricase nanoparticles (Nplex) was formed to achieve the delivery of BmK9 and uricase, respectively. The formulation of Nplex has a diameter of 180 nm and drug loading up to 200%, which releases BmK9 and uricase slowly and steadily in drug release tests in vitro. There was significantly improved pharmacokinetic behavior of the two drugs because Nplex prolonged the half-life and increased tissue accumulation. Histological assessments showed that the dual drug Nplex can reduce the inflammation response in acute gouty arthritis and chronic uric acid nephropathy in vivo. In the macrophage system, there was lower toxicity and increased beneficial effect on inflammation with Nplex than free BmK9 or uricase. Collectively, this novel formulation provides a dual drug delivery system that can treat gouty arthritis and uric acid nephropathy.

scholarly journals Factor XII Activation Promotes Platelet Consumption in the Presence of Bacterial-Type Long-Chain Polyphosphate In Vitro and In Vivo

2018 ◽  
Vol 38 (8) ◽  
pp. 1748-1760 ◽  
Author(s):  
Jevgenia Zilberman-Rudenko ◽  
Stéphanie E. Reitsma ◽  
Cristina Puy ◽  
Rachel A. Rigg ◽  
Stephanie A. Smith ◽  
...  
Keyword(s):  
Factor Xii ◽  
Bacterial Type ◽  
Long Chain

Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

2021 ◽  
Author(s):  
Catherine Karbasiafshar ◽  
Frank W. Sellke ◽  
M. Ruhul Abid
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Treatment Options ◽  
Current Treatment ◽  
Lifestyle Changes ◽  
Challenges And Opportunities ◽  
Artery Disease ◽  
New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

Abstract 372: The Endothelial Glycocalyx Promotes Homogenous Blood Flow Distribution within the Microvasculature

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
P Mason McClatchey
Keyword(s):  
Fluid Dynamics ◽  
Blood Flow ◽  
Blood Viscosity ◽  
Tissue Perfusion ◽  
Microvascular Perfusion ◽  
Endothelial Glycocalyx ◽  
Heterogeneous Distribution ◽  
Disease States

Introduction: Impaired tissue oxygenation is observed in many disease states including congestive heart failure, diabetes, cancer and aging. Decreased tissue perfusion and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. We hypothesized that microfluidic properties of the glycocalyx would promote perfusion homogeneity. Methods: To test our hypothesis, we used established empirical formulations for modelling blood viscosity in vivo (blood vessels) and in vitro (glass tubes). We first assess distribution of blood flow in idealized arteriolar networks. We next simulated distribution of blood flow at an idealized capillary bifurcation. Finally, we simulated velocity profiles and pressure gradients within the vessel lumen with varying glycocalyx properties using a computational fluid dynamics approach. Results: We found that transit time heterogeneity (as assessed by STD to mean ratio) was increased approximately 9x (6.9x-10.6x) using in vitro formulations of blood viscosity relative to in vivo formulations. This effect was mathematically accounted for by increased effective blood viscosity in smaller arterioles. We also found that distribution of blood flow at an idealized microvascular bifurcation was more symmetric using the in vivo formulation than the in vitro formulation (approximately 2x greater disparity between flow in downstream vessels). This effect was mathematically accounted for by an increased hematocrit dependence of blood viscosity. Both the diameter- and hematocrit-based changes in blood viscosity were entirely predictable from fluid dynamics simulations incorporating a space-filling, semi-permeable glycocalyx layer. Summary: Our simulations indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Conclusions: The literature provides evidence of both glycocalyx degradation and impaired tissue perfusion in the same disease states. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a wide variety of diseases.

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