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Endothelium

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This article is about the lining of blood and lymphatic vessels. For the endothelium of the cornea, seecorneal endothelium.
Endothelium
Diagram showing the location of endothelial cells
Transmissionelectron micrographof amicrovesselshowing endothelial cells, which encircle anerythrocyte(E), forming the innermost layer of the vessel, thetunica intima.
Details
SystemCirculatory system
LocationLining of the inner surface ofblood vesselsandlymphatic vessels
Identifiers
MeSHD004727
THH2.00.02.0.02003
FMA63916
Anatomical terms of microanatomy

Theendothelium(pl.:endothelia) is a single layer ofsquamousendothelial cellsthat line the interior surface ofblood vesselsandlymphatic vessels.[1]The endothelium forms an interface between circulatingbloodorlymphin thelumenand 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 withlymphare known as lymphatic endothelial cells. Vascular endothelial cells line the entirecirculatory system,from theheartto the smallestcapillaries.

These cells have unique functions that includefluid filtration,such as in theglomerulusof the kidney,blood vessel tone,hemostasis,neutrophilrecruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is calledendocardium.An impaired function can lead to serious health issues throughout the body.

Structure[edit]

The endothelium is a thin layer of single flat (squamous) cells that line the interior surface ofblood vesselsandlymphatic vessels.[1]

Endothelium is ofmesodermalorigin. Both blood and lymphaticcapillariesare composed of a single layer of endothelial cells called a monolayer. In straight sections of a blood vessel, vascular endothelial cells typically align and elongate in the direction of fluid flow.[2][3]

Terminology[edit]

Thefoundational model of anatomy,an index of terms used to describe anatomical structures, makes a distinction between endothelial cells andepithelial cellson the basis of which tissues they develop from, and states that the presence ofvimentinrather thankeratinfilaments separates these from epithelial cells.[4]Many considered the endothelium a specializedepithelialtissue.[5]

Function[edit]

Endothelium lines the inner wall of vessels, shown here.
Microscopic viewshowing endothelium (at top) inside theheart.

The endothelium forms an interface between circulatingbloodorlymphin thelumenand the rest of the vessel wall. This forms a barrier between vessels and tissues and control the flow of substances and fluid into and out of a tissue. This controls the passage of materials and the transit ofwhite blood cellsinto and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelium, as in cases of chronic inflammation, may lead to tissue swelling (edema). Altered barrier function is also implicated in cancer extravasation.[6]

Endothelial cells are involved in many other aspects of vessel function, including:

Blood vessel formation[edit]

The endothelium is involved in the formation of new blood vessels, calledangiogenesis.[11]Angiogenesis is a crucial process for development of organs in the embryo and fetus,[12]as well as repair of damaged areas.[13]The process is triggered by decreased tissue oxygen (hypoxia) or insufficient oxygen tension leading to the new development of blood vessels lined with endothelial cells. Angiogenesis is regulated by signals that promote and decrease the process. These pro- and antiangiogenic signals including integrins, chemokines, angiopoietins, oxygen sensing agents, junctional molecules and endogenous inhibitors.[12]Angiopoietin-2works with VEGF to facilitate cell proliferation and migration of endothelial cells.

The general outline of angiogenesis is

  • activating signals binding to surface receptors of vascular endothelial cells.
  • activated endothelial cells release proteases leading to the degradation of the basement membrane
  • endothelial cells are freed to migrate from the existing blood vessels and begin to proliferate to form extensions towards the source of the angiogenic stimulus.

Host immune response[edit]

Endothelial cells express a variety of immune genes in an organ-specific manner.[14]These genes include criticalimmune mediatorsand proteins that facilitatecellular communicationwith hematopoietic immune cells.[15]Endothelial cells encode important features of the structural cell immune response in theepigenomeand can therefore respond swiftly to immunological challenges. The contribution to host immunity by non-hematopoietic cells, such as endothelium, is called “structural immunity”.[16]

Clinical significance[edit]

Main article:Endothelial dysfunction

Endothelial dysfunction,or the loss of proper endothelial function, is a hallmark for vascular diseases, and is often regarded as a key early event in the development ofatherosclerosis.[17]Impaired endothelial function, causing hypertension and thrombosis, is often seen in patients withcoronary artery disease,diabetes mellitus,hypertension,hypercholesterolemia,as well as insmokers.Endothelial dysfunction has also been shown to be predictive of future adverse cardiovascular events including stroke, heart disease, and is also present in inflammatory disease such as rheumatoid arthritis, diabetes, and systemic lupus erythematosus.[18][19]

Endothelial dysfunction is a result of changes in endothelial function.[20][21]After fat (lipid) accumulation and when stimulated by inflammation, endothelial cells become activated, which is characterized by the expression of molecules such as E-selectin, VCAM-1 and ICAM-1, which stimulate the adhesion of immune cells.[22]Additionally,transcription factors,which are substances which act to increase the production of proteins within cells, become activated; specifically AP-1 andNF-κB,leading to increased expression of cytokines such asIL-1,TNFαandIFNγ,which promotes inflammation.[23][24]This state of endothelial cells promotes accumulation of lipids and lipoproteins in the intima, leading to atherosclerosis, and the subsequent recruitment of white blood cells and platelets, as well as proliferation of smooth muscle cells, leading to the formation of a fatty streak. The lesions formed in the intima, and persistent inflammation lead to desquamation of endothelium, which disrupts the endothelial barrier, leading to injury and consequent dysfunction.[25]In contrast, inflammatory stimuli also activate NF-κB-induced expression of the deubiquitinase A20 (TNFAIP3), which has been shown to intrinsically repair the endothelial barrier.[26]

One of the main mechanisms of endothelial dysfunction is the diminishing ofnitric oxide,often due to high levels ofasymmetric dimethylarginine,which interfere with the normalL-arginine-stimulatednitric oxide synthesisand so leads to hypertension. The most prevailing mechanism of endothelial dysfunction is an increase inreactive oxygen species,which can impair nitric oxide production and activity via several mechanisms.[27]The signalling proteinERK5is essential for maintaining normal endothelial cell function.[28]A further consequence of damage to the endothelium is the release of pathological quantities ofvon Willebrand factor,which promote platelet aggregation and adhesion to the subendothelium, and thus the formation of potentially fatal thrombi.

Angiosarcomais cancer of the endothelium and is rare with only 300 cases per year in the US.[29]However it generally has poor prognosis with a five-year survival rate of 35%.[30]

Research[edit]

Endothelium in cancer[edit]

It has been recognised that endothelial cells building tumour vasculature have distinct morphological characteristics, different origin compared to physiological endothelium, and distinct molecular signature, which gives an opportunity for implementation of new biomarkers of tumour angiogenesis and could provide new anti-angiogenic druggable targets.[31]

Endothelium in diet[edit]

Ahealthy dietabundant in fruits and vegetables has a beneficial impact on endothelial function, whilst a diet high inredandprocessed meats,fried foods,refined grainsandprocessed sugarincreases adhesion endothelial cells and atherogenic promoters.[32]High-fat diets adversely affect the endothelial function.[33]

AMediterranean diethas been found to improve endothelial function in adults which can reduce risk of cardiovascular disease.[34][35]Walnutconsumption improves endothelial function.[36][37]

Endothelium in Covid-19[edit]

In April 2020, the presence of viral elements in endothelial cells of 3 patients who had died ofCOVID-19was reported for the first time. The researchers from theUniversity of ZurichandHarvard Medical Schoolconsidered these findings to be a sign of a generalendotheliitisin different organs, an inflammatory response of the endothelium to the infection that can lead or at least contribute to multi-organ failure in Covid-19 patients with comorbidities such as diabetes mellitus, hypertension and cardiovascular disease.[38][39]

History[edit]

In 1865, theSwissanatomistWilhelm Hisfirst coin the term “endothelium”.[40]In 1958, A. S. Todd of theUniversity of St Andrewsdemonstrated that endothelium in human blood vessels have fibrinolytic activity.[41][42]

See also[edit]

List of distinct cell types in the adult human body

References[edit]

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External links[edit]

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