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Glycoprotein VI
Glycoprotein VI (platelet), also known as GPVI, is a glycoprotein receptor for collagen which is expressed in platelets. In humans, glycoprotein VI is encoded by the ''GPVI'' gene. GPVI was first cloned in 2000 by several groups including that of Martine Jandrot-Perrus from INSERM. Function Glycoprotein VI (GP6) is a 58-kD platelet membrane glycoprotein that plays a crucial role in the collagen-induced activation and aggregation of platelets. Upon injury to the vessel wall and subsequent damage to the endothelial lining, exposure of the subendothelial matrix to blood flow results in deposition of platelets. Collagen fibers are the most thrombogenic macromolecular components of the extracellular matrix, with collagen types I, III, and VI being the major forms found in blood vessels. Platelet interaction with collagen occurs as a 2-step procedure: (1) the initial adhesion to collagen is followed by (2) an activation step leading to platelet secretion, recruitment of additional pl ...
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Glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secreted extracellular proteins are often glycosylated. In proteins that have segments extending extracellularly, the extracellular segments are also often glycosylated. Glycoproteins are also often important integral membrane proteins, where they play a role in cell–cell interactions. It is important to distinguish endoplasmic reticulum-based glycosylation of the secretory system from reversible cytosolic-nuclear glycosylation. Glycoproteins of the cytosol and nucleus can be modified through the reversible addition of a single GlcNAc residue that is considered reciprocal to phosphorylation and the functions of these are likely to be an additional regulatory mechanism that controls phosphorylation-based signalling. In contra ...
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Collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole-body protein content. Collagen consists of amino acids bound together to form a triple helix of elongated fibril known as a collagen helix. It is mostly found in connective tissue such as cartilage, bones, tendons, ligaments, and skin. Depending upon the degree of mineralization, collagen tissues may be rigid (bone) or compliant (tendon) or have a gradient from rigid to compliant (cartilage). Collagen is also abundant in corneas, blood vessels, the gut, intervertebral discs, and the dentin in teeth. In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes one to two percent of muscle tissue and accounts for 6% of the weight of the skeletal muscle tissue. The fibroblast is the most common ...
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Platelets
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow or lung, which then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site of interrupted endothelium. They gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activ ...
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Gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as ...
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Endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues thr ...
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Thrombogenicity
Thrombogenicity refers to the tendency of a material in contact with the blood to produce a thrombus, or clot. It not only refers to fixed thrombi but also to emboli, thrombi which have become detached and travel through the bloodstream. Thrombogenicity can also encompass events such as the activation of immune pathways and the complement system. All materials are considered to be thrombogenic with the exception of the normal state of endothelial cells which line blood vessels. Certain medical implants appear non-thrombogenic due to high flow rates of blood past the implant, but in reality all are thrombogenic to a degree. Various surface treatments are available to minimize these thrombogenic effects. A thrombogenic implant will eventually be covered by a fibrous capsule, the thickness of this capsule can be considered one measure of thrombogenicity, and if extreme can lead to the failure of the implant. See also * Endothelial activation Endothelial activation is a proinflam ...
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Platelet Plug
The platelet plug, also known as the hemostatic plug or platelet thrombus, is an aggregation of platelets formed during early stages of hemostasis in response to one or more injuries to blood vessel walls. After platelets are recruited and begin to accumulate around the breakage, their “sticky” nature allows them to adhere to each other. This forms a platelet plug, which prevents more blood from leaving the body as well as any outside contaminants from getting in. The plug provides a temporary blockage of the break in the vasculature. As such, platelet plug formation occurs after vasoconstriction of the blood vessels but before the creation of the fibrin mesh clot, which is the more permanent solution to the injury. The result of the platelet plug formation is the coagulation of blood. It can also be referred to as primary hemostasis. History For many years, the critical role that platelets (also known as thrombocytes) played in hemostasis and blood coagulation went unnot ...
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Atherosclerotic Plaque
An atheroma, or atheromatous plaque, is an abnormal and reversible accumulation of material in the inner layer of an arterial wall. The material consists of mostly macrophage cells, or debris, containing lipids, calcium and a variable amount of fibrous connective tissue. The accumulated material forms a swelling in the artery wall, which may intrude into the lumen of the artery, narrowing it and restricting blood flow. Atheroma is the pathological basis for the disease entity atherosclerosis, a subtype of arteriosclerosis. Signs and symptoms For most people, the first symptoms result from atheroma progression within the heart arteries, most commonly resulting in a heart attack and ensuing debility. The heart arteries are difficult to track because they are small (from about 5 mm down to microscopic), they are hidden deep within the chest and they never stop moving. Additionally, all mass-applied clinical strategies focus on both minimal cost and the overall safety ...
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Collagen Receptor
Collagen receptors are membrane proteins that bind the extracellular matrix protein collagen, the most abundant protein in mammals. They control mainly cell proliferation, migration and adhesion, coagulation cascade activation and they affect ECM structure by regulation of MMP (matrix metalloproteinases). There are at least eight human collagen receptors. Platelet membrane glycoproteins Platelet membrane glycoproteins, mainly GPIa/IIa, GPVI and probably GPIV as well, function as receptors engaged in platelet adhesion to collagen. The leading role in the elimination of high-stress injury is taken by the glycoprotein Ib-IX-V complex. Integrins Integrins function as the major cell receptor for extracellular matrix protein. These receptors comprise an α and β transmembrane subunit, which are noncovalently bound. Collagen binding is primarily provided by integrins α1β1, α2β1, α10β1 and α11β1. Integrin α1β1 binds to collagen via the MIDAS motif in the α subunit I doma ...
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