FibrinogenFibrinogen）It is a glycoprotein synthesized and secreted by liver cells（αtwoβtwoγ2) It is an important protein and fibrin in the process of coagulation and hemostasis.[1]It is a monomer protein generated by thrombin in the process of blood coagulation, which removes fibrinogen A and B from blood fibrinogen.High fibrinogen is a variety ofThrombotic diseases Important risk factors are considered as markers of disease status in clinical practice.
Fibrinogen is a protein with coagulation function, which is mainly synthesized by liver cells. It is the highest coagulation factor in plasma.The molecular weight of fibrinogen is about 340kDa, which is triple spherical and consists ofα、β、γIt is composed of three pairs of different polypeptide chains, with D region at both ends and E region in the middleαSpiral peptide chains are connected.Fibrinogen isThrombosisIt is an important reaction substrate that participates in the key steps of thrombosis.Fibrinogen in thrombin, blood fiber stabilizing factor (FX Ⅲ a), Ca2+It forms fibrin monomer under the action of other coagulation factors, and covalently combines with each other to form fibrin polymerαThe chains cross overlap and covalently cross link to form a stable fibrin network, which eventually includes red blood cells (RBC), platelets (PLT)α2 - Anti fibrinolytic enzyme（α2-AP) and other components form stable thrombus structure.[2]
Action mechanism
Announce
edit
Hemostatic chart
When platelets rupture, they will release clotting activating enzyme, which catalyzes prothrombin to become thrombin under the action of calcium ion. Thrombin coagulates the water-soluble fibrinogen in the plasma into insoluble fibrin, which kinks other blood cells into clusters and becomes clots.Fibrinogen (factor I) is a glycoprotein circulating in the blood of vertebrates.In the organization andVascular injuryDuring this period, it is enzymatically converted into fibrin by thrombin, and then converted into fibrin based blood clots.Fibrinogen mainly plays the role of blocking blood vessels, thus preventing excessive bleeding.However, fibrin, the product of fibrinogen, binds and reduces the activity of thrombin.This activity, sometimes called antithrombin I, is used to limit blood clotting.The loss or reduction of this antithrombin 1 activity due to mutations in the fibrinogen gene or low fibrinogen conditions can lead to excessive blood coagulation and thrombosis.Fibrin also mediates platelet andendothelial cellsDiffusion, OrganizationalFibroblastProliferation, capillary formation and angiogenesis play a role in promoting tissue blood supply reconstruction, wound healing and tissue repair.
structure
Announce
edit
Fibrinogen includes Aα、Bβ、γPolypeptide chain, each peptide chain consists of 610, 461 and 411Amino acid residueComposition.The molecular weight of fibrinogen is 340kD, the plasma concentration is 2-4g/L, and the half-life is nearly 4 days.The central domain of fibrinogen is called "E domain", and the expanded spherical domain formed at the end is called "D domain".[3]
Fibrinogen is encoded by three independent genes.Code Aα、BβChainγThe polypeptide chain genes are located in the long arm of chromosome 4 (4q23-4q32), with a length of about 50kb;Where AαThe gene has five exons, BβGenes andγAll genes have 8 exons.[3]
effect
Announce
edit
Fibrinogen can promote platelet aggregation, promote the growth, proliferation and contraction of smooth muscle and endothelial cells, increase blood viscosity and peripheral resistance, cause endothelial cell damage, promote collagen and DNA synthesis, chemotactic monocyte/macrophage migration to the inner membrane, promote erythrocyte adhesion and thrombosis, therefore,It plays an important role in the pathogenesis of cardiovascular diseases.
Clinical significance
Announce
edit
Clinical data show that: ① Most patients with elevated fibrinogen level may have myocardial infarction or sudden death, and the higher the fibrinogen level, the greater the risk; ②The increase of plasma fibrinogen is an important factor to promote the pathogenesis of atherosclerosis; ③Fibrinogen increases, blood is in hypercoagulable state, blood flow speed slows down, blood viscosity increases, and thrombus is easy to occur; ④Hypertension is often accompanied by an increase in fibrinogen level, which is an important reason for inducing and aggravating hypertension; ⑤Fibrinogen is closely related to fat metabolism; ⑥In addition, the elderly, smoking, obesity, stressOral contraceptivesAnd diabetes can increase the level of fibrinogen in the body.[4]
Research on fibrinogen related drugs
Announce
edit
Fibrinogen receptor antagonist
Fibrinogen and platelet receptor are GP Ⅱ b/Ⅲ a. Fibrinogen receptor antagonists act as the final pathway of platelet aggregation, blocking the binding of fibrinogen and GP Ⅱ b/Ⅲ a receptor on platelets, inhibiting platelet aggregation, playing a role in prolonging clotting time and inhibiting the formation of blood clots.[5]
As shown in the figure Fibrinogen Receptor Antagonists:
Fibrinogen receptor antagonist
Fibrinolytic agent
FibrinolysisThe agent mainly inhibits the formation of thrombus in two ways: on the one hand, it reduces the content of fibrinogen in the blood, inhibits platelet aggregation and adhesion, improves blood rheology, and inhibits the formation of thrombus.On the other hand, it decomposes fibrinogen, and the decomposition products stimulate endothelial cells to secrete t-PA, activate the body's fibrinolytic system, and play a role in reducing fibrinogen content and thrombolysis.[5]
