Effect of fibrin degradation products on fibrinolytic process

Yatsenko, Tetiana; Rybachuk, V. М.; Yusova, O. I.; Kharchenko, S. M.; Grinenko, T. V.

doi:10.15407/ubj88.02.016

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…Some researchers have shown high plasminogen activation stimulation ability of fibrin crosslinked fragment DD [4,14,16,25], whereas in other publications [15,26] plasminogen interaction with DD-fragment was not confirmed. The present work is a clear explanation of the data differences -we have shown that the usage of calcium-binding agents (EDTA, sodium citrate etc.)…”

Section: Fig 1 Sds-page (8%) Analysis Of Fibrinogen and Fibrin Fragmentioning

confidence: 99%

Ca(2+)-dependent regulation of fibrinolytic system activation on fibrin(ogen) D-domains

Yatsenko¹,

Rybachuk²,

Kharchenko³

et al. 2017

Ukr.Biochem.J

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In the present study, we investigated whether calcium content modulation in D-domains of fibrin(ogen) was involved in fibrinolytic process activation. To investigate the effect of Caibrinogen plays a key role in blood coagulation by forming the polymer fibrin lattice of blood clot in case of blood vessels trauma. Plasminogen activation in response to fibrin formation promotes plasmin generation and clot dissolution. The impairing of clotting/fibrinolytic balance causes a wide range of cardiovascular diseases which cure requires the understanding of mechanisms of clotting and fibrinolytic system interactions.Fibrinogen is a 340 kDa symmetrical dimeric protein with three pairs of polypeptide chains -(Аα, Вβ, γ) 2 -linked together by disulfide bonds. The fibrinogen molecule contains two distal C-terminal D regions (each consists of independently folded β-and γ-nodules) linked by coiled-coils to central E region, which is formed by amino termini of all six polypeptide chains. Two C-terminal αC-domains link to coiled-coils beyond D regions by α-chain connector [1]. Under polymerization, fibrinogen molecule undergoes structural changes: thrombin cleavage of fibrinopeptides from E-domain leads to formation there of A and B polymerization sites, which interact with complement a and b polymerization sites (knob-to-hole interaction) in D-domains of two other fibrin molecules providing protofibril formation. Fibrin structure is stabilized when C-terminal parts of Aα-chains and two adjacent fibrin molecules Ddomains are covalently cross-linked by factor XIIIa.The fibrinogen molecule has several important binding sites relating to its function. Two sets of high-affinity binding sites for both tissue-type plasminogen activator and plasminogen, which play an important role in the initiation of fibrinolysis, are located on the αC-domain and the peripheral D-domain [2]. These sites are hidden in the intact fibrinogen and exposed in fibrin during polymerization. In D-domain knob-to-hole interactions provide conformational changes and only known Aα 148-160 plasminogen binding region and γ 312-324 tPA-binding region become uncovered and bind proenzyme and its activator initiating fibrinolytic system activation and plasmin formation [3].Fibrinogen has both strong and weak binding sites for calcium ions, which are important for its

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Section: Fig 1 Sds-page (8%) Analysis Of Fibrinogen and Fibrin Fragmentioning

confidence: 99%

Ca(2+)-dependent regulation of fibrinolytic system activation on fibrin(ogen) D-domains

Yatsenko¹,

Rybachuk²,

Kharchenko³

et al. 2017

Ukr.Biochem.J

Self Cite

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“…4 FDPs include fibrinogen degradation products (FgDPs) and cross-linked fibrin degradation products (FbDPs). 5,6 The former are the products of fibrinogen (Fib) and fibrin monomer (FM), while the latter include the products of D-dimer and other fragments. 6 An elevated level of FDP indicates hyperfibrinolysis activity, including primary hyperfibrinolysis and secondary hyperfibrinolysis.…”

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confidence: 99%

Identification of and solution for false D‐dimer results

Zhang

et al. 2020

Clinical Laboratory Analysis

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Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials

Pagar

Musale

Pawar

et al. 2022

ACS Biomater. Sci. Eng.

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In recent decades there has been growing interest of material chemists in the successful development of functional materials for drug delivery, tissue engineering, imaging, diagnosis, theranostic, and other biomedical applications with advanced nanotechnology tools. The efficacy and safety of functional materials are determined by their pharmacological, toxicological, and immunogenic effects. It is essential to consider all degradation pathways of functional materials and to assess plausible intermediates and final products for quality control. This review provides a brief insight into chemical degradation mechanisms of functional materials like oxidation, photodegradation, and physical and enzymatic degradation. The intermediates and products of degradation were confirmed with analytical methods such as proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), UV–vis spectroscopy (UV–vis), infrared spectroscopy (IR), differential scanning calorimetry (DSC), mass spectroscopy, and other sophisticated analytical methods. These analytical methods are also used for regulatory, quality control, and stability purposes in industry. The assessment of degradation is important to predetermine the behavior of functional materials in specific storage conditions and can be relevant to their behavior during in vivo applications. Another important aspect is the evaluation of the toxicity of functional materials. Toxicity can be accessed with various methods using in vitro, in vivo, ex vivo, and in silico models. In vitro cell culture methods are used to determine mitochondrial damage, reactive oxygen species, stress responses, and cellular toxicity. In vitro cellular toxicity can be measured by MTT assay, LDH leakage assay, and hemolysis. In vivo studies are performed using various animal models involving zebrafish, rodents (mice and rats), and nonhuman primates. Ex vivo studies are also used for efficacy and toxicity determinations of functional materials like ex vivo potency assay and precision-cut liver slice (PCLS) models. The in silico tools with computational simulations like quantitative structure–activity relationships (QSAR), pharmacokinetics (PK) and pharmacodynamics (PD), dose and time response, and quantitative cationic–activity relationships ((Q)CARs) are used for prediction of the toxicity of functional materials. In this review, we studied the principle methods used for degradation studies, different degradation pathways, and mechanisms of functional material degradation with prototype examples. We discuss toxicity assessments with different toxicity approaches used for estimation of the safety and efficacy of functional materials.

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Effect of fibrin degradation products on fibrinolytic process

Cited by 5 publications

References 17 publications

Ca(2+)-dependent regulation of fibrinolytic system activation on fibrin(ogen) D-domains

Ca(2+)-dependent regulation of fibrinolytic system activation on fibrin(ogen) D-domains

Identification of and solution for false D‐dimer results

Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials

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