endothelium

{{Short description|Layer of cells that line the inner surface of blood vessels}}

{{about|the lining of blood and lymphatic vessels|the endothelium of the cornea|corneal endothelium}}

{{Infobox cell

| Name = Endothelium

| Latin =

| Image = Microscopic anatomy of an artery en.svg

| Caption = Diagram showing the location of endothelial cells

| Image2 = Microvessel.jpg

| Caption2 = Transmission electron micrograph of a microvessel showing endothelial cells, which encircle an erythrocyte (E), forming the innermost layer of the vessel, the tunica intima.

| Precursor =

| System = Circulatory system

| Location = Lining of the inner surface of blood vessels and lymphatic vessels

}}

The endothelium ({{plural form}}: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels.{{DorlandsDict|three/000035470|Endothelium}} The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall.

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 throughout the body.

Structure

The endothelium is a thin layer of single flat (squamous) cells that line the interior surface of blood vessels and lymphatic vessels.

Endothelium is of mesodermal origin. Both blood and lymphatic capillaries are 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.{{cite journal |author3-link=Larry McIntire | vauthors = Eskin SG, Ives CL, McIntire LV, Navarro LT | title = Response of cultured endothelial cells to steady flow | journal = Microvascular Research | volume = 28 | issue = 1 | pages = 87–94 | date = July 1984 | pmid = 6748961 | doi = 10.1016/0026-2862(84)90031-1 }}{{cite journal | vauthors = Langille BL, Adamson SL | title = Relationship between blood flow direction and endothelial cell orientation at arterial branch sites in rabbits and mice | journal = Circulation Research | volume = 48 | issue = 4 | pages = 481–488 | date = April 1981 | pmid = 7460219 | doi = 10.1161/01.RES.48.4.481 | doi-access = free }}

= Terminology =

The foundational model of anatomy, an index of terms used to describe anatomical structures, makes a distinction between endothelial cells and epithelial cells on the basis of which tissues they develop from, and states that the presence of vimentin rather than keratin filaments separates these from epithelial cells.{{cite web|url=http://bioportal.bioontology.org/ontologies/FMA/?p=classes&conceptid=http%3A%2F%2Fsig.uw.edu%2Ffma%23Endothelial_cell&jump_to_nav=true |title=Endothelial cell | work = BioPortal | publisher = Stanford University |access-date=2013-09-28 |url-status=dead |archive-url=https://web.archive.org/web/20131002075249/http://bioportal.bioontology.org/ontologies/FMA/?p=classes&conceptid=http%3A%2F%2Fsig.uw.edu%2Ffma%23Endothelial_cell&jump_to_nav=true |archive-date=2013-10-02 }} Many considered the endothelium a specialized epithelial tissue.{{cite journal | vauthors = Kovacic JC, Mercader N, Torres M, Boehm M, Fuster V | title = Epithelial-to-mesenchymal and endothelial-to-mesenchymal transition: from cardiovascular development to disease | journal = Circulation | volume = 125 | issue = 14 | pages = 1795–1808 | date = April 2012 | pmid = 22492947 | pmc = 3333843 | doi = 10.1161/circulationaha.111.040352 | author1-link = Jason Kovacic }} However, much research uncovered not only similarities but also differences between endothelia and epithelia. {{cite journal

| doi-access = free}} The comparison is further complicated by the diversity that endothelial cells exhibit. {{cite journal | last1 = Trimm | first1 = Emily | last2 = Red-Horse | first2 = Kristy | title = Vascular endothelial cell development and diversity | journal = Nature Reviews Cardiology | volume = 20 | issue = 3 | pages = 197–210 | year = 2023 | doi = 10.1038/s41569-022-00770-1 | url = https://doi.org/10.1038/s41569-022-00770-1 | issn = 1759-5010 | pmc = 9533272 }}

Function

File:2104 Three Major Capillary Types.jpg

File:Endocardium and subendocardium histology.png showing endothelium (at top) inside the heart.]]

The endothelium forms an interface between circulating blood or lymph in the lumen and 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 of white blood cells into 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.{{cite journal | vauthors = Escribano J, Chen MB, Moeendarbary E, Cao X, Shenoy V, Garcia-Aznar JM, Kamm RD, Spill F | display-authors = 6 | title = Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation | journal = PLOS Computational Biology | volume = 15 | issue = 5 | pages = e1006395 | date = May 2019 | pmid = 31048903 | pmc = 6497229 | doi = 10.1371/journal.pcbi.1006395 | arxiv = 1811.09326 | bibcode = 2019PLSCB..15E6395E | doi-access = free }}

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

Blood clotting (thrombosis and fibrinolysis). Under normal conditions, the endothelium provides a surface on which blood does not clot, because it contains and expresses substances that prevent clotting,{{Citation |last=Félétou |first=Michel |title=Multiple Functions of the Endothelial Cells |date=2011 |work=The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators |url=https://www.ncbi.nlm.nih.gov/books/NBK57148/ |access-date=2024-05-20 |publisher=Morgan & Claypool Life Sciences |language=en}} including heparan sulfate which acts as a cofactor for activating antithrombin, a protein that inactivates several factors in the coagulation cascade.{{Cite journal |last=Weitz |first=Jeffrey I. |date=2003-04-01 |title=Heparan sulfate: Antithrombotic or not? |journal=Journal of Clinical Investigation |volume=111 |issue=7 |pages=952–954 |doi=10.1172/JCI200318234 |issn=0021-9738 |pmid=12671043|pmc=152594 }}
Inflammation.{{cite journal | vauthors = Li X, Fang P, Li Y, Kuo YM, Andrews AJ, Nanayakkara G, Johnson C, Fu H, Shan H, Du F, Hoffman NE, Yu D, Eguchi S, Madesh M, Koch WJ, Sun J, Jiang X, Wang H, Yang X | display-authors = 6 | title = Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 36 | issue = 6 | pages = 1090–1100 | date = June 2016 | pmid = 27127201 | pmc = 4882253 | doi = 10.1161/ATVBAHA.115.306964 }} Endothelial cells actively signal to white blood cells of the immune system{{cite journal | vauthors = Vestweber D | title = How leukocytes cross the vascular endothelium | journal = Nature Reviews. Immunology | volume = 15 | issue = 11 | pages = 692–704 | date = November 2015 | pmid = 26471775 | doi = 10.1038/nri3908 | s2cid = 29703333 }} during inflammation
Formation of new blood vessels (angiogenesis).
Constriction and enlargement of the blood vessel, called vasoconstriction and vasodilation, and hence the control of blood pressure

=Blood vessel formation=

The endothelium is involved in the formation of new blood vessels, called angiogenesis.{{Cite journal |last1=Griffioen |first1=A. W. |last2=Molema |first2=G. |date=2000 |title=Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation |journal=Pharmacological Reviews |volume=52 |issue=2 |pages=237–268 |pmid=10835101}} Angiogenesis is a crucial process for development of organs in the embryo and fetus, as well as repair of damaged areas.{{cite journal | pmid=37060495 | date=2023 | last1=Dudley | first1=A. C. | last2=Griffioen | first2=A. W. | title=Pathological angiogenesis: Mechanisms and therapeutic strategies | journal=Angiogenesis | volume=26 | issue=3 | pages=313–347 | doi=10.1007/s10456-023-09876-7 | pmc=10105163 }} 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.{{cite journal | vauthors = Bouïs D, Kusumanto Y, Meijer C, Mulder NH, Hospers GA | title = A review on pro- and anti-angiogenic factors as targets of clinical intervention | journal = Pharmacological Research | volume = 53 | issue = 2 | pages = 89–103 | date = February 2006 | pmid = 16321545 | doi = 10.1016/j.phrs.2005.10.006 }} Angiopoietin-2 works 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 =

Endothelial cells express a variety of immune genes in an organ-specific manner.{{cite journal | vauthors = Krausgruber T, Fortelny N, Fife-Gernedl V, Senekowitsch M, Schuster LC, Lercher A, Nemc A, Schmidl C, Rendeiro AF, Bergthaler A, Bock C | display-authors = 6 | title = Structural cells are key regulators of organ-specific immune responses | journal = Nature | volume = 583 | issue = 7815 | pages = 296–302 | date = July 2020 | pmid = 32612232 | pmc = 7610345 | doi = 10.1038/s41586-020-2424-4 | s2cid = 220295181 | doi-access = free | bibcode = 2020Natur.583..296K }} These genes include critical immune mediators and proteins that facilitate cellular communication with hematopoietic immune cells.{{cite journal | vauthors = Armingol E, Officer A, Harismendy O, Lewis NE | title = Deciphering cell-cell interactions and communication from gene expression | journal = Nature Reviews. Genetics | volume = 22 | issue = 2 | pages = 71–88 | date = February 2021 | pmid = 33168968 | pmc = 7649713 | doi = 10.1038/s41576-020-00292-x }} Endothelial cells encode important features of the structural cell immune response in the epigenome and can therefore respond swiftly to immunological challenges. The contribution to host immunity by non-hematopoietic cells, such as endothelium, is called “structural immunity”.{{cite journal | vauthors = Minton K | title = A gene atlas of 'structural immunity' | journal = Nature Reviews. Immunology | volume = 20 | issue = 9 | pages = 518–519 | date = September 2020 | pmid = 32661408 | doi = 10.1038/s41577-020-0398-y | s2cid = 220491226 | doi-access = free }}

Clinical significance

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 of atherosclerosis.{{cite journal | vauthors = Botts SR, Fish JE, Howe KL | title = Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment | journal = Frontiers in Pharmacology | volume = 12 | pages = 787541 | date = December 2021 | pmid = 35002720 | pmc = 8727904 | doi = 10.3389/fphar.2021.787541 | doi-access = free }} Impaired endothelial function, causing hypertension and thrombosis, is often seen in patients with coronary artery disease, diabetes mellitus, hypertension, hypercholesterolemia, as well as in smokers. 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.{{cite journal | vauthors = Tsukahara T, Tsukahara R, Haniu H, Matsuda Y, Murakami-Murofushi K | title = Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma | journal = Molecular and Cellular Endocrinology | volume = 412 | pages = 320–329 | date = September 2015 | pmid = 26007326 | doi = 10.1016/j.mce.2015.05.021 | hdl = 10069/35888 | s2cid = 10454566 | hdl-access = free }}{{cite journal | vauthors = Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, Nishigaki I | title = The vascular endothelium and human diseases | journal = International Journal of Biological Sciences | volume = 9 | issue = 10 | pages = 1057–1069 | date = 2013-11-09 | pmid = 24250251 | pmc = 3831119 | doi = 10.7150/ijbs.7502 }}

Endothelial dysfunction is a result of changes in endothelial function.{{cite journal | vauthors = Iantorno M, Campia U, Di Daniele N, Nistico S, Forleo GB, Cardillo C, Tesauro M | title = Obesity, inflammation and endothelial dysfunction | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 28 | issue = 2 | pages = 169–176 | date = April 2014 | pmid = 25001649 }}{{cite journal | vauthors = Reriani MK, Lerman LO, Lerman A | title = Endothelial function as a functional expression of cardiovascular risk factors | journal = Biomarkers in Medicine | volume = 4 | issue = 3 | pages = 351–360 | date = June 2010 | pmid = 20550469 | pmc = 2911781 | doi = 10.2217/bmm.10.61 }} 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.{{cite journal | vauthors = Lopez-Garcia E, Hu FB | title = Nutrition and the endothelium | journal = Current Diabetes Reports | volume = 4 | issue = 4 | pages = 253–259 | date = August 2004 | pmid = 15265466 | doi = 10.1007/s11892-004-0076-7 | s2cid = 24878288 }} Additionally, transcription factors, which are substances which act to increase the production of proteins within cells, become activated; specifically AP-1 and NF-κB, leading to increased expression of cytokines such as IL-1, TNFα and IFNγ, which promotes inflammation.{{cite journal | vauthors = Blake GJ, Ridker PM | title = Inflammatory bio-markers and cardiovascular risk prediction | journal = Journal of Internal Medicine | volume = 252 | issue = 4 | pages = 283–294 | date = October 2002 | pmid = 12366601 | doi = 10.1046/j.1365-2796.2002.01019.x | s2cid = 26400610 | doi-access = free }}{{cite journal | vauthors = Mizuno Y, Jacob RF, Mason RP | title = Inflammation and the development of atherosclerosis | journal = Journal of Atherosclerosis and Thrombosis | volume = 18 | issue = 5 | pages = 351–358 | date = 2011 | pmid = 21427505 | doi = 10.5551/jat.7591 | doi-access = free }} 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.{{cite journal | vauthors = Mäyränpää MI, Heikkilä HM, Lindstedt KA, Walls AF, Kovanen PT | title = Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion | journal = Coronary Artery Disease | volume = 17 | issue = 7 | pages = 611–621 | date = November 2006 | pmid = 17047445 | doi = 10.1097/01.mca.0000224420.67304.4d | s2cid = 1884596 }} 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.{{cite journal | vauthors = Soni D, Wang DM, Regmi SC, Mittal M, Vogel SM, Schlüter D, Tiruppathi C | title = Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury | journal = Cell Death Discovery | volume = 4 | issue = 60 | pages = 60 | date = May 2018 | pmid = 29796309 | pmc = 5955943 | doi = 10.1038/s41420-018-0056-3 }}

One of the main mechanisms of endothelial dysfunction is the diminishing of nitric oxide, often due to high levels of asymmetric dimethylarginine, which interfere with the normal L-arginine-stimulated nitric oxide synthesis and so leads to hypertension. The most prevailing mechanism of endothelial dysfunction is an increase in reactive oxygen species, which can impair nitric oxide production and activity via several mechanisms.{{cite journal | vauthors = Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ | display-authors = 6 | title = Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension | journal = Journal of Hypertension | volume = 23 | issue = 1 | pages = 7–17 | date = January 2005 | pmid = 15643116 | doi = 10.1097/00004872-200501000-00004 }} The signalling protein ERK5 is essential for maintaining normal endothelial cell function.{{cite journal | vauthors = Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ | title = ERK5 and the regulation of endothelial cell function | journal = Biochemical Society Transactions | volume = 37 | issue = Pt 6 | pages = 1254–1259 | date = December 2009 | pmid = 19909257 | doi = 10.1042/BST0371254 }} A further consequence of damage to the endothelium is the release of pathological quantities of von Willebrand factor, which promote platelet aggregation and adhesion to the subendothelium, and thus the formation of potentially fatal thrombi.

Angiosarcoma is cancer of the endothelium and is rare with only 300 cases per year in the US.{{Cite web|date=2019-02-27|title=Angiosarcoma - National Cancer Institute|url=https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-vascular-tumors/angiosarcoma|access-date=2021-08-10|website=www.cancer.gov|language=en}} However it generally has poor prognosis with a five-year survival rate of 35%.{{cite journal | vauthors = Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ | title = Angiosarcoma | journal = The Lancet. Oncology | volume = 11 | issue = 10 | pages = 983–991 | date = October 2010 | pmid = 20537949 | doi = 10.1016/S1470-2045(10)70023-1 }}

= Research =

= Endothelium in cancer =

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.* {{cite book | vauthors = Milosevic V, Edelmann RJ, Fosse JH, Östman A, Akslen LA | chapter = Molecular Phenotypes of Endothelial Cells in Malignant Tumors. | veditors = Akslen LA, Watnick RS | title = Biomarkers of the Tumor Microenvironment | year = 2022 | pages = 31–52 | publisher = Springer | location = Cham | doi = 10.1007/978-3-030-98950-7_3 | isbn = 978-3-030-98949-1 }}

=Endothelium in diet=

A healthy diet abundant in fruits and vegetables has a beneficial impact on endothelial function, whilst a diet high in red and processed meats, fried foods, refined grains and processed sugar increases adhesion endothelial cells and atherogenic promoters.{{cite journal | vauthors = Defagó MD, Elorriaga N, Irazola VE, Rubinstein AL | title = Influence of food patterns on endothelial biomarkers: a systematic review | journal = Journal of Clinical Hypertension | volume = 16 | issue = 12 | pages = 907–913 | date = December 2014 | pmid = 25376124 | pmc = 4270900 | doi = 10.1111/jch.12431 }} High-fat diets adversely affect the endothelial function.{{cite journal | vauthors = Fewkes JJ, Kellow NJ, Cowan SF, Williamson G, Dordevic AL | title = A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis | journal = The American Journal of Clinical Nutrition | volume = 116 | issue = 3 | pages = 699–729 | date = September 2022 | pmid = 35665799 | pmc = 9437993 | doi = 10.1093/ajcn/nqac153 }}

A Mediterranean diet has been found to improve endothelial function in adults which can reduce risk of cardiovascular disease.{{cite journal | vauthors = Shannon OM, Mendes I, Köchl C, Mazidi M, Ashor AW, Rubele S, Minihane AM, Mathers JC, Siervo M | display-authors = 6 | title = Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | journal = The Journal of Nutrition | volume = 150 | issue = 5 | pages = 1151–1159 | date = May 2020 | pmid = 32027740 | doi = 10.1093/jn/nxaa002 | doi-access = free }}{{cite journal | vauthors = Fatima K, Rashid AM, Memon UA, Fatima SS, Javaid SS, Shahid O, Zehri F, Obaid MA, Ahmad M, Almas T, Minhas AM | display-authors = 6 | title = Mediterranean Diet and its Effect on Endothelial Function: A Meta-analysis and Systematic Review | journal = Irish Journal of Medical Science | volume = 192| issue = 1| date = February 2022 | pages = 105–113 | pmid = 35192097 | doi = 10.1007/s11845-022-02944-9 | pmc = 9892125 | s2cid = 247013758 | doi-access = free }} Walnut consumption improves endothelial function.{{cite journal | vauthors = Mohammadi-Sartang M, Bellissimo N, Totosy de Zepetnek JO, Bazyar H, Mahmoodi M, Mazloom Z | title = Effects of walnuts consumption on vascular endothelial function in humans: A systematic review and meta-analysis of randomized controlled trials | journal = Clinical Nutrition ESPEN | volume = 28 | issue = | pages = 52–58 | date = December 2018 | pmid = 30390893 | doi = 10.1016/j.clnesp.2018.07.009 | s2cid = 53221430 }}{{cite journal | vauthors = Xiao Y, Huang W, Peng C, Zhang J, Wong C, Kim JH, Yeoh EK, Su X | display-authors = 6 | title = Effect of nut consumption on vascular endothelial function: A systematic review and meta-analysis of randomized controlled trials | journal = Clinical Nutrition | volume = 37 | issue = 3 | pages = 831–839 | date = June 2018 | pmid = 28457654 | doi = 10.1016/j.clnu.2017.04.011 | s2cid = 13930609 }}

= Endothelium in Covid-19 =

In April 2020, the presence of viral elements in endothelial cells of 3 patients who had died of COVID-19 was reported for the first time. The researchers from the University of Zurich and Harvard Medical School considered these findings to be a sign of a general endotheliitis in 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.{{cite journal | vauthors = Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H | display-authors = 6 | title = Endothelial cell infection and endotheliitis in COVID-19 | journal = Lancet | volume = 395 | issue = 10234 | pages = 1417–1418 | date = May 2020 | pmid = 32325026 | pmc = 7172722 | doi = 10.1016/S0140-6736(20)30937-5 }}{{cite journal | vauthors = Sardu C, Gambardella J, Morelli MB, Wang X, Marfella R, Santulli G | title = Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence | journal = Journal of Clinical Medicine | volume = 9 | issue = 5 | page = 1417 | date = May 2020 | pmid = 32403217 | pmc = 7290769 | doi = 10.3390/jcm9051417 | doi-access = free }}

History

In 1865, the Swiss anatomist Wilhelm His Sr. first coined the term “endothelium”.{{Citation |last=Félétou |first=Michel |title=Introduction |date=2011 |work=The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators |url=https://www.ncbi.nlm.nih.gov/books/NBK57145/ |access-date=2024-05-20 |publisher=Morgan & Claypool Life Sciences |language=en}} In 1958, A. S. Todd of the University of St Andrews demonstrated that endothelium in human blood vessels have fibrinolytic activity.{{cite journal | vauthors = Todd AS | title = Fibrinolysis autographs | journal = Nature | volume = 181 | issue = 4607 | pages = 495–496 | date = February 1958 | pmid = 13517190 | doi = 10.1038/181495b0 | s2cid = 4219257 | bibcode = 1958Natur.181..495T | eissn = 1476-4687 }}{{cite journal | vauthors = Todd AS | title = Localization of Fibrinolytic Activity in Tissues | journal = British Medical Bulletin | volume = 20 | issue = 3 | pages = 210–212 | date = September 1964 | pmid = 14209761 | doi = 10.1093/oxfordjournals.bmb.a070333 | eissn = 1471-8391 }}

References

External links

{{UCDavisOrganology|Circulatory/vessels/capillaries1/capillaries3}}, "Capillaries, non-fenestrated (EM, Low)"
{{BUHistology|21402ooa}}

Category:Angiology

Category:Tissues (biology)