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Polskie Archiwum Medycyny Wewnetrznej Sep 2011Acquired qualitative abnormalities of fibrinogen molecules, termed acquired dysfibrinogenemia, have been demonstrated in several disease states mostly related to... (Review)
Review
Acquired qualitative abnormalities of fibrinogen molecules, termed acquired dysfibrinogenemia, have been demonstrated in several disease states mostly related to prothrombotic tendency, including multiple myeloma and liver disease. Fibrin is abundant in atherosclerotic plaques. Altered plasma fibrin properties, reflected usually by reduced clot permeability and impaired fibrinolysis, have been reported in patients with acute or prior myocardial infarction, ischemic stroke, and peripheral artery disease. Moreover, prothrombotic clot phenotype has been observed in patients with previous no-reflow phenomenon and stent thrombosis. Growing evidence indicates that acquired dysfibrinogenemia contributes to the progression of atherosclerotic vascular disease and the occurrence of its thrombotic manifestations. The review summarizes current knowledge on the links between fibrin clot phenotype and atherosclerotic vascular disease and describes a wide spectrum of cardiovascular risk factors as modifiers of fibrin network characteristics.
Topics: Atherosclerosis; Fibrin; Fibrinogens, Abnormal; Humans; Plaque, Atherosclerotic; Risk Factors
PubMed: 21952526
DOI: No ID Found -
Experimental Cell Research Oct 2013In vitro models of endothelial assembly into microvessels are useful for the study of angiogenesis and vasculogenesis. In addition, such models may be used to provide... (Review)
Review
In vitro models of endothelial assembly into microvessels are useful for the study of angiogenesis and vasculogenesis. In addition, such models may be used to provide the microvasculature required to sustain engineered tissues. A large range of in vitro models of both angiogenesis and vasculogenesis have utilized fibrin gel as a scaffold. Although fibrin gel is conducive to endothelial assembly, its ultrastructure varies substantially based on the gel formulation and gelation conditions, making it challenging to compare between models. This work reviews existing models of endothelial assembly in fibrin gel and posits that differerences between models are partially caused by microstructural differences in fibrin gel.
Topics: Animals; Cell Differentiation; Endothelium, Vascular; Fibrin; Gels; Humans; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 23800466
DOI: 10.1016/j.yexcr.2013.06.006 -
Critical Reviews in Oncology/hematology 1989This review addresses the question of the involvement of fibrin in the development of atherosclerotic plaques. Numerous studies in the older literature demonstrated the... (Review)
Review
This review addresses the question of the involvement of fibrin in the development of atherosclerotic plaques. Numerous studies in the older literature demonstrated the presence of fibrinogen and/or fibrin in plaques, but the techniques that were available (mainly immunochemistry and immunohistochemistry with polyclonal antifibrinogen antibodies) did not clearly distinguish fibrinogen from fibrin or fibrinogen/fibrin degradation products. Some of these studies suggested that the fibrinogen-related protein within lesions resulted from incorporation of thrombi into lesions, while other studies suggested that fibrinogen itself entered the vessel wall. Newer studies by the authors and collaborators used specific antibodies for various fibrinopeptides to quantitate fibrinogen, fibrin I, fibrin II, and fragment X in thrombi and different histologic types of plaques. These studies showed that normal aortas contained fibrinogen and that fatty and fibrous plaques contained fibrinogen, fibrin I, and fibrin II, while complicated plaques contained fibrin II and fragment X, indicating a progression from fibrinogen to fibrin and fibrinogen/fibrin degradation products in parallel with increasing severity of the lesions. Later studies by the authors and collaborators used a sensitive immunohistochemical technique with monoclonal antibodies to demonstrate the distribution of fibrinogen-related antigens. Patterns suggesting incorporation of thrombi were seen, as were patterns suggesting formation of fibrin in association with arterial wall monocyte/macrophages and smooth muscle cells. The data from these various studies suggest the possibility that fibrin formation occurs within the arterial wall and contributes to plaque formation.
Topics: Antigens; Arteriosclerosis; Endothelium, Vascular; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Immunochemistry; Immunohistochemistry; Thrombosis
PubMed: 2688680
DOI: 10.1016/s1040-8428(89)80016-2 -
Colloids and Surfaces. B, Biointerfaces Aug 2021Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor...
Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin sealants, do not provide an optimal environment for native cell proliferation and subsequent tissue regeneration. Therefore, new treatments outside the confines of these conventional fibrin bulk gel therapies are required. We have previously developed flowable, low-density fibrin nanoparticles that, when coupled to keratinocyte growth factor, promote cell migration and epithelial wound closure in vivo. Here, we report a new high throughput method for generating the fibrin nanoparticles using probe sonication, which is less time intensive than the previously reported microfluidic method, and investigate the ability of the sonicated fibrin nanoparticles (SFBN) to promote clot formation and cell migration in vitro. The SFBNs can form a fibrin gel when combined with fibrinogen in the absence of exogenous thrombin, and the polymerization rate and fiber density in these fibrin clots is tunable based on SFBN concentration. Furthermore, fibrin gels made with SFBNs support cell migration in an in vitro angiogenic sprouting assay, which is relevant for wound healing. In this report, we show that SFBNs may be a promising wound healing therapy that can be easily produced and delivered in a flowable formulation.
Topics: Fibrin; Fibrin Tissue Adhesive; Nanoparticles; Polymerization; Wound Healing
PubMed: 33964527
DOI: 10.1016/j.colsurfb.2021.111805 -
Proceedings of the National Academy of... Mar 2021Fibrin is the main component of blood clots. The mechanical properties of fibrin are therefore of critical importance in successful hemostasis. One of the divalent...
Fibrin is the main component of blood clots. The mechanical properties of fibrin are therefore of critical importance in successful hemostasis. One of the divalent cations released by platelets during hemostasis is Zn; however, its effect on the network structure of fibrin gels and on the resultant mechanical properties remains poorly understood. Here, by combining mechanical measurements with three-dimensional confocal microscopy imaging, we show that Zn can tune the fibrin network structure and alter its mechanical properties. In the presence of Zn, fibrin protofibrils form large bundles that cause a coarsening of the fibrin network due to an increase in fiber diameter and reduction of the total fiber length. We further show that the protofibrils in these bundles are loosely coupled to one another, which results in a decrease of the elastic modulus with increasing Zn concentrations. We explore the elastic properties of these networks at both low and high stress: At low stress, the elasticity originates from pulling the thermal slack out of the network, and this is consistent with the thermal bending of the fibers. By contrast, at high stress, the elasticity exhibits a common master curve consistent with the stretching of individual protofibrils. These results show that the mechanics of a fibrin network are closely correlated with its microscopic structure and inform our understanding of the structure and physical mechanisms leading to defective or excessive clot stiffness.
Topics: Elastic Modulus; Fibrin; Humans; Rheology; Zinc
PubMed: 33649231
DOI: 10.1073/pnas.2020541118 -
Molecular Medicine (Cambridge, Mass.) 2011Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as... (Review)
Review
Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, Bβ15-42 in particular possesses potential antiinflammatory effects. Bβ15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.
Topics: Animals; Fibrin; Fibrinogen; Fibrinopeptide A; Fibrinopeptide B; Humans; Inflammation; Models, Biological
PubMed: 21210072
DOI: 10.2119/molmed.2010.00146 -
Journal of Thrombosis and Haemostasis :... Feb 2003This review covers the functional features of the fibrinogen gamma chains including their participation in fibrin polymerization and cross-linking, their role in the... (Review)
Review
This review covers the functional features of the fibrinogen gamma chains including their participation in fibrin polymerization and cross-linking, their role in the initiation of fibrinolysis, their binding and regulation of factor XIII activity, their interactions with platelets and other cells, and their role in mediating thrombin binding to fibrin, a thrombin inhibitory function termed 'antithrombin I'.
Topics: Binding Sites; Blood Platelets; Cross-Linking Reagents; Fibrin; Fibrinogen; Fibrinolysis; Humans; Integrins; Peptide Fragments; Plasminogen; Tissue Plasminogen Activator
PubMed: 12871494
DOI: 10.1046/j.1538-7836.2003.00063.x -
TheScientificWorldJournal 2015Due to the increasing needs for organ transplantation and a universal shortage of donated tissues, tissue engineering emerges as a useful approach to engineer functional... (Review)
Review
Due to the increasing needs for organ transplantation and a universal shortage of donated tissues, tissue engineering emerges as a useful approach to engineer functional tissues. Although different synthetic materials have been used to fabricate tissue engineering scaffolds, they have many limitations such as the biocompatibility concerns, the inability to support cell attachment, and undesirable degradation rate. Fibrin gel, a biopolymeric material, provides numerous advantages over synthetic materials in functioning as a tissue engineering scaffold and a cell carrier. Fibrin gel exhibits excellent biocompatibility, promotes cell attachment, and can degrade in a controllable manner. Additionally, fibrin gel mimics the natural blood-clotting process and self-assembles into a polymer network. The ability for fibrin to cure in situ has been exploited to develop injectable scaffolds for the repair of damaged cardiac and cartilage tissues. Additionally, fibrin gel has been utilized as a cell carrier to protect cells from the forces during the application and cell delivery processes while enhancing the cell viability and tissue regeneration. Here, we review the recent advancement in developing fibrin-based biomaterials for the development of injectable tissue engineering scaffold and cell carriers.
Topics: Biocompatible Materials; Fibrin; Gels; Humans; Tissue Engineering; Tissue Scaffolds
PubMed: 25853146
DOI: 10.1155/2015/685690 -
Bulletin of Mathematical Biology Mar 2021During the hemostatic phase of wound healing, vascular injury leads to endothelial cell damage, initiation of a coagulation cascade involving platelets, and formation of...
During the hemostatic phase of wound healing, vascular injury leads to endothelial cell damage, initiation of a coagulation cascade involving platelets, and formation of a fibrin-rich clot. As this cascade culminates, activation of the protease thrombin occurs and soluble fibrinogen is converted into an insoluble polymerized fibrin network. Fibrin polymerization is critical for bleeding cessation and subsequent stages of wound healing. We develop a cooperative enzyme kinetics model for in vitro fibrin matrix polymerization capturing dynamic interactions among fibrinogen, thrombin, fibrin, and intermediate complexes. A tailored parameter subset selection technique is also developed to evaluate parameter identifiability for a representative data curve for fibrin accumulation in a short-duration in vitro polymerization experiment. Our approach is based on systematic analysis of eigenvalues and eigenvectors of the classical information matrix for simulations of accumulating fibrin matrix via optimization based on a least squares objective function. Results demonstrate robustness of our approach in that a significant reduction in objective function cost is achieved relative to a more ad hoc curve-fitting procedure. Capabilities of this approach to integrate non-overlapping subsets of the data to enhance the evaluation of parameter identifiability are also demonstrated. Unidentifiable reaction rate parameters are screened to determine whether individual reactions can be eliminated from the overall system while preserving the low objective cost. These findings demonstrate the high degree of information within a single fibrin accumulation curve, and a tailored model and parameter subset selection approach for improving optimization and reducing model complexity in the context of polymerization experiments.
Topics: Animals; Cells, Cultured; Fibrin; Humans; Kinetics; Models, Biological; Polymerization; Wound Healing
PubMed: 33751272
DOI: 10.1007/s11538-021-00876-6 -
Structure (London, England : 1993) Jun 2018The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically...
The space-filling fibrin network is a major part of clots and thrombi formed in blood. Fibrin polymerization starts when fibrinogen, a plasma protein, is proteolytically converted to fibrin, which self-assembles to form double-stranded protofibrils. When reaching a critical length, these intermediate species aggregate laterally to transform into fibers arranged into branched fibrin network. We combined multiscale modeling in silico with atomic force microscopy (AFM) imaging to reconstruct complete atomic models of double-stranded fibrin protofibrils with γ-γ crosslinking, A:a and B:b knob-hole bonds, and αC regions-all important structural determinants not resolved crystallographically. Structures of fibrin oligomers and protofibrils containing up to 19 monomers were successfully validated by quantitative comparison with high-resolution AFM images. We characterized the protofibril twisting, bending, kinking, and reversibility of A:a knob-hole bonds, and calculated hydrodynamic parameters of fibrin oligomers. Atomic structures of protofibrils provide a basis to understand mechanisms of early stages of fibrin polymerization.
Topics: Crystallography, X-Ray; Fibrin; Microscopy, Atomic Force; Models, Molecular; Protein Conformation; Protein Multimerization
PubMed: 29754827
DOI: 10.1016/j.str.2018.04.005