Review the mechanisms by which endothelial cells contribute to inflammation in key diseases
The endothelium is a cell layer that is lined on the interior surface of lymphatic vessels and blood vessels, which are made up of endothelial cells (Dorland, 2012).
The endothelial cells in direct contact with blood cells are called vascular endothelial cells while those in contact with lymph are called lymphatic endothelial cells.
Besides regulating hemostasis, endothelial cells also possess important functions like permeability, regulation of vascular tone, immunity, leukocyte trafficking, inflammation and angiogenesis among others.[1][2][3].
Inflammation is the reaction of the body's tissue to an injury, fundamental in the innate and adaptive response. Signs of inflammation are characterised as rubor, dolor, tumor and calor, meaning redness, pain, swelling and heat respectively. The benefits of inflammation outweighs the adverse effects and is important for survival although too much inflammation might cause harm, like sepsis or septic shock[4].
The process of inflammation contributed by endothelial cells starts with endothelial hyperpermeability when mediated by inflammatory agonists. The increase in permeability allows for transendothelial migration for cells like leukocytes.
The entire process starts off when an agonist involved is bound to receptors specific to it, expressed on the endothelial cell surface, activating enzymes like phospholipase C (PLC) directly through vascular endothelial growth factor receptors (VEGFR) or by thrombin or histamine through G protein coupled receptors (GPCR).
Once binding has occurred, a cascade of signalling reactions will initiate, with Rho guanosine-5'-triphosphate (Rho GTPases) such as rho-asso...
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...n of the valves. ClfA mediates the attachment to nonbacterial thrombotic endocarditis (NBTE) followed by FnbpA causing endothelial cell internalisation, inflammatory and coagulation responses[12].
The fibronectin which is a ligand for fibronectin-binding protein expressing bacteria binds to the integrins, expressed by the inflamed endothelial cells, causing increased adhesion susceptibility , tissue necrosis, inflammation and vegetation growth.
In conclusion, endothelial cells in atherosclerosis causes the increased expression of surface adhesion molecules which results in the increased amount of leukocytes attracted to the site and thus causing more inflammation than usual. In infective endocarditis, NBTE allows bacterial adhesion of the heart valves, mediated by ClfA and then FnbpA. These causes a range of reactions spanning of vegetative growth to inflammation.
Margination and adhesion to the endothelium, in which accumulation of leukocytes occurs along the endothelial wall for adhesion. Afterward, these adhesions cause the separation of endothelial cells, allowing the leukocytes to extend and Transmigrate through the vessel walls. Followed by the response of chemical mediators(chemotaxis) that influence cell migration via an energy directed process which triggers the activation of Phagocytosis, in which monocytes, neutrophils, and tissue macrophages are activated to engulf and degrade cellular debris and
...s to interfere with bonding to the receptors. The final possibility uses CNP, which downregulates the activation in MAP kinase pathways in the chondrocytes (4).
Researchers think that this immune system response may be triggered by bacteria or viruses, material in the intestinal contents, or a defective signal from the body’s own cells, called an autoimmune response. Inflammation results in pain, heat, redness, and swelling of the tissue. Chronic inflammation can harm the function of tissues and organs (U.S. News, 2009). Crohn’s disease also appears to affect certain ethnic groups more than others. American Jews of European descent are four to five times more likely to de... ...
The walls of arteries are made up of three layers same as veins. Its inner endothelium is composed of epithelial cells which is very smooth. This layer helps minimise the friction. The tunica media provides strength and elasticity. It contains smooth muscles, collagen and large amount of elastic fibres.
Atherosclerosis begins when the inner wall of the artery becomes damaged and cholesterol and fatty plaques begin to lodge in the arteries. Damage to the endothelial wall inside the artery can be caused by hypertension, hyperlipidemia, and hyperglycemia (“Subclinical Atherosclerosis..” 443). When this happens, the immune system responds by sending monocytes to the damaged area. The monocytes turn into macrophages; their job is to eat up the excess cholesterol and unblock the artery. The macrophages are unable to digest all of the cholesterol, and as a result turn in to foam cells. When many macrophages are turned into foam cells, plaque results, and protrudes into the arterial wall, restricting blood flow and raising blood pressure (“Atherosclerosis Growth Process.” 8). If the plaque becomes too large it may break, releasing plaque into the blood. This can cause a great reduction in blood flow or a clot, resulting in stroke or myocardial infarction (“Stroke Risk.” 3).
Epithelia tissue : Epithelial tissue, the type of tissue that lines the surfaces and cavities of your body 's organs, epithelia may be composed of several layers of cells called compound epithelia or just a single layer known as simple epithelia.
The lymphatic system is a network of lymphatic vessels that is a blunt-ended linear system in which lymph (a fluid comprised of tissue fluids, cells and large extracellular molecules) is returned to the bloodstream. The lymphatic system is one of the body’s defenses against illness and disease. It is sometimes included as part of the circulatory system and includes the immune
bacteria can spread to the heart and arteries causing life threatening problems. It is obvious that
Atherosclerosis is a disease in which plaque builds up inside the arteries. Arteries are blood vessels that carry oxygen-rich blood to the heart and other parts of your body. It develops by the accumulation of excess Low Density Lipoprotein (LDL) in the arterial wall causing damage to the vascular endothelium which increases expression of adhesion molecules that latch onto monocytes and T cells and decreases the ability of the endothelial cells to release Nitric oxide (NO). Monocytes and LDL accumulates at the site of injury then penetrates the intima where monocytes differenciate to become macrophages and the ...
...-1 (PAI-1) from the endothelial cells and monocytes, activating the extrinsic coagulation pathway. This also leads to activation of factor X and fibrin production.
The inflammatory response is a nonspecific response to cellular injury and bacterial invasion. Inflammation is the primary defense in early gingivitis. Biofilm can initiate an inflammatory response if it is left undisturbed for as little as seventy two hours. Redness and swelling are two of the cardinal signs of inflammation and can be observed clinically in gingivitis. Histamine is released by mast cells and responsible for the redness and swelling of tissues. Histamine causes both an increase in vascularity and permeability of blood vessels at the site of injury. Swelling may occur in response to the accumulation of fluid at a specific site. The inflammatory response includes cellular components of the immune system polymorphonuclear leukocytes and macrophages. Polymorphonuclear leukocytes are crucial to the cellular immune response. Polyporphonuclear leukocytes are the first cells that arrive at an inflammatory site. Polymorphonuclear leukocytes arrive at the site via chemotaxis, and begin to phagocytize bacteria. As the disease continues and the inflammatory reaction is not strong enough to subside the bacterial infection the immune response is further
The Circulatory System is a transportation and cooling system for the body. The Red Blood Cells act like billions of little mail men carrying all kinds of things that are needed by the cells, also RBC's carry oxygen and nutrients to the cells. All cells in the body require oxygen to remain alive. Also there is another kind of cells called white blood cells moving in the system. Why blood cells protect from bacteria and other things that are harmful. The Circulatory system contains vein arteries, veins are used to carry blood to the heart and arteries to carry the blood away. The blood inside veins is where most of the oxygen and nutrients are and is called deoxygenated and the color of the blood is dark red. However, blood in the arteries are also full of oxygen but is a bright red. The main components of the circulatory system are the heart, blood, and blood vessels.
To clearly understand the correlation between abnormalities of cilia and cardiovascular pathology, knowing the mechanism behind mechanosensory role of cilia is crucial. A few mechanisms have been proposed [5, 91]. We have already discussed the mechanism involving down-regulation of surviving in formation of aneurysm. Another mechanism involves polycystin-1 and polycystin-2, an 11 transmembrane protein with a long extracellular domain and a cation channel with 6 transmembrane domains respectively. Endothelial cells without cilia were isolated from Tg737 mice to examine the mechanosensory role of cilia. To confirm polycystin-1 and polycystin-2 as mechanosensory proteins, endothelial cells were collected from PKD mice and human patients. Polycystins are absent in the cilia of these cells and present in Tg737 mice cells, but localized at the base of clilia.
The system contains the fluid lymph that flows within lymphatic vessels. The system also consists of
Innate system critical main defense is the cellular component; there are several kinds of cells involved in the process. One of the crucial cells is the macrophage. ...