The Multifactorial Model of Cardiovascular Pathology: Is Caffeine Pathogenic in Coronary Heart Disease?
Barry D. Smith, Uma Gupta, B.S. Gupta in Caffeine and Activation Theory, 2006
Further examinations of heritability have included molecular genetic studies using functional genomic methodology in an attempt to identify specific genes that may code for CHD. For example, high levels of fibrinogen have been found to predict future coronary heart disease. Fibrinogen is a large glycoprotein, which is a clotting factor that serves to activate thrombin and aggregate platelets. Variants of the h-fibrinogen gene subunit on 4q28 are associated with these elevated levels (Yang et al., 2005), though further research is needed to establish a direct causal link to CHD (G. Smith, Harbord, Milton, Ebrahim, & Sterne, 2005). Another genetic study focused on the involvement of the renin–angiotensin system (RAS) in premature CHD risk. Higher frequencies of the angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms contributed to increased CHD risk, and the ACE genotype may thus be a risk factor (Sekuri et al., 2005).
The Acute Phase Response: An Overview
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
Mannan-binding protein (MBP) is an acute phase lectin with specificity for terminal nonreducing N-acetylglucosamine, mannose, fucose, and glucose residues,20,21 which are present in a number of pathogens. MBP has structural similarities to Clq and conglutinin,22 and activates the complement system through either the classical23 or the alternative pathway,24 thereby serving as an opsonin. Complement is a major effector system consisting of more than 30 proteins. The complement components, many of which are acute phase reactants, can, on activation, affect chemotaxis, opsonization, vascular permeability, and vascular dilation, and can lead to cytotoxicity. Fibrinogen plays a major role in hemostasis, tissue repair, and wound healing.25 Fibrinogen binds to activated platelets, forming interplatelet bridges which restore the structural integrity of injured blood vessels.26 Fibrinogen and fibrin interact with endothelial cells, promoting the adhesion, motility, and cytoskeletal organization of these cells.27
Blood Coagulation and Fibrinolysis in TTP and HUS
Pia Glas-Greenwalt in Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
The routine laboratory tests of hemostasis are normal or near normal in most patients with TTP and HUS. In fact, marked prolongation of the prothrombin time (PT) or activated partial thromboplastin time (aPTT), abnormally decreased levels of fibrinogen, and/or the presence of fibrin/ogen split products should cast doubt upon the diagnosis of TTP/HUS. However, profound alterations of these laboratory tests can be found in patients with advanced disease and superimposed disseminated intravascular coagulation.11-14 In our series of 31 patients with TTP/HUS, the PT at diagnosis was abnormal (prothrombin ratio >1.2) in nine, but in no case was the ratio higher than 1.5. The fibrinogen concentration was 360 ±180 mg/dl (mean ± S.D.) with no value below 150 mg/dl. In fact, the fibrinogen levels were abnormally high in nearly half the patients, perhaps owing to its characteristics as an acute-phase reactant. The absence of consumptive coagulopathy was settled in studies with labeled fibrinogen, in which a normal turnover rate for this protein had been observed.15,16 The fibrin/ogen split products found in some patients with uncomplicated TTP/HUS have been ascribed to an enhanced release of plasminogen activator by the damaged endothelium rather than to an increased cleavage of fibrinogen by thrombin.8 Isolated prolongations of the aPTT have been reported in patients with thrombotic microangiopathy associated with the antiphospholipid syndrome.17
Branch retinal vein occlusion following cataract surgery
Published in Clinical and Experimental Optometry, 2018
Silvio Polizzi, Francesco Barca, Tomaso Caporossi, Gianni Virgili, Stanislao Rizzo
Our patient had several risk factors for BRVO: systemic hypertension, moderately elevated levels of homocysteine, previous BRVO in the fellow eye, numerous arteriovenous crossings and local narrowing of the veins that, leading to venous stasis in blood flow, could lead to venous occlusion. She also had slightly elevated levels of D‐dimer and fibrinogen. D‐dimer is the primary degradation product of cross‐linked fibrin. It reflects ongoing activation of the haemostatic system and it is elevated in several acute thrombotic disorders. Fibrinogen is a soluble protein in the plasma that is broken down to fibrin by the enzyme thrombin to form clots. It plays a controversial role in the pathogenesis of BRVO. A population‐based, cross‐sectional study of 6,147 participants from six US communities showed that both D‐dimer and fibrinogen were not significantly associated with BRVO.2008
Potent Hemostatic Efficacy of a Novel Recombinant Fibrin Sealant Patch (KTF-374) in Rabbit Bleeding Models
Published in Journal of Investigative Surgery, 2019
Sumika Miyabashira (Tanaka), Takayuki Imamura, Miho Fujimoto, Akitoshi Ohno, Tsunefumi Kobayashi, Noriko Shinya
KTF-374 consists of two layers, a fibrinogen layer and a thrombin layer. The fibrinogen layer is applied to the bleeding site. Because the fibrinogen layer is highly soluble and promptly dissolves upon application, it may increase the local concentration of fibrinogen at the active surface. This is thought to react with thrombin that flows down from the thrombin layer, producing a fibrin clot with high hemostatic efficacy. This hypothesis is supported by the finding by Shinya et al. that fibrin sealants have strong adhesive properties when fibrinogen solution is rubbed into the site of application.14 The adhesion between fibrinogen and tissue is increased by binding of adhesive glycoproteins,15 thus enhancing the tissue-anchoring effect of fibrin sealant. Meanwhile, the formation of cross-linked fibrinogen γ-chain was observed in SDS-PAGE analysis performed after dissolution of the fibrin clot formed after application of KTF-374 to porcine blood (data not shown). Although KTF-374 does not contain coagulation factor XIII, it likely reacted with coagulation factor XIII in the blood of the laboratory animals to form cross-linked fibrinogen and fibrin gel.
Current and emerging biologics for the treatment of hemophilia
Published in Expert Opinion on Biological Therapy, 2019
Giancarlo Castaman, Silvia Linari
Hemostasis begins with vasoconstriction and the accumulation of platelets at the site of injury. Although circulating platelets are normally quiescent, everything changes when vascular injury occurs. Platelets tumble along the exposed surface, intermittently detained by interaction between their surface glycoprotein Ibα and von Willebrand factor (VWF) in the subendothelial matrix, and finally adhere to collagen via two receptors, one that binds collagen tightly (integrin α2β1) in a position to interact with a second low-affinity receptor (glycoprotein VI) that transmits a stimulus to the cell [25]. This triggers different reactions that convert the quiescent platelet membrane glycoprotein complex IIb/IIIa into an active binding site for fibrinogen and stimulate the cells to release ADP, thromboxane A2 and serotonin, which activate other platelets. Fibrinogen is a large, adhesive bivalent protein that cross-links neighboring platelets into aggregates to begin building a hemostatic plug.
Related Knowledge Centers
- Bleeding
- Enzyme
- Fibrin
- Endothelium
- Platelet
- Glycoprotein
- Thrombus
- Fibroblast
- Protein Complex
- Thrombin