Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact withlymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entirecirculatory system, from theheart to the smallestcapillaries.
These cells have unique functions that includefluid filtration, such as in theglomerulus of the kidney,blood vessel tone,hemostasis,neutrophil recruitment, 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.
Endothelium is ofmesodermal origin. Both blood and lymphaticcapillaries 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.[2][3]
Thefoundational model of anatomy, an index of terms used to describe anatomical structures, makes a distinction between endothelial cells andepithelial cells on the basis of which tissues they develop from, and states that the presence ofvimentin rather thankeratin filaments separates these from epithelial cells.[4] Many considered the endothelium a specializedepithelial tissue.[5] However, much research uncovered not only similarities but also differences between endothelia and epithelia.[6] The comparison is further complicated by the diversity that endothelial cells exhibit.[7]
Endothelium lines the inner wall of vessels, shown here.Microscopic view showing endothelium (at top) inside theheart.
The endothelium forms an interface between circulatingblood orlymph in thelumen and the rest of the vessel wall. This forms a barrier between vessels and tissues and controls the flow of substances and fluid into and out of a tissue. This controls the passage of materials and the transit ofwhite 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.[8]
Endothelial cells are involved in many other aspects of vessel function, including:
Blood clotting (thrombosis andfibrinolysis). Under normal conditions, the endothelium provides a surface on which blood does not clot, because it contains and expresses substances that prevent clotting,[9] includingheparan sulfate which acts as acofactor for activatingantithrombin, a protein that inactivates several factors in the coagulation cascade.[10]
Inflammation.[11] Endothelial cells actively signal to white blood cells of the immune system[12] during inflammation
The endothelium is involved in the formation of new blood vessels, calledangiogenesis.[13] Angiogenesis is a crucial process for development of organs in the embryo and fetus,[14] as well as repair of damaged areas.[15] 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.[14]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.
Endothelial cells express a variety of immune genes in an organ-specific manner.[16] These genes include criticalimmune mediators and proteins that facilitatecellular communication with hematopoietic immune cells.[17] Endothelial cells encode important features of the structural cell immune response in theepigenome and can therefore respond swiftly to immunological challenges. The contribution to host immunity by non-hematopoietic cells, such as endothelium, is called "structural immunity".[18]
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.[19] 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.[20][21]
Endothelial dysfunction is a result of changes in endothelial function.[22][23] 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.[24] 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,TNFα andIFNγ, which promotes inflammation.[25][26] 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.[27] 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.[28]
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 synthesis and 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.[29] The signalling proteinERK5 is essential for maintaining normal endothelial cell function.[30] 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.
Angiosarcoma is cancer of the endothelium and is rare with only 300 cases per year in the US.[31] However it generally has poor prognosis with a five-year survival rate of 35%.[32]
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.[33]
Ahealthy diet abundant in fruits and vegetables has a beneficial impact on endothelial function, whilst a diet high inred andprocessed meats, fried foods,refined grains andprocessed sugar increases adhesion endothelial cells and atherogenic promoters.[34] High-fat diets adversely affect the endothelial function.[35]
AMediterranean diet has been found to improve endothelial function in adults which can reduce risk of cardiovascular disease.[36][37]Walnut consumption improves endothelial function.[38][39]
In April 2020, the presence of viral elements in endothelial cells of 3 patients who had died ofCOVID-19 was reported for the first time. The researchers from theUniversity of Zurich andHarvard Medical School considered these findings to be a sign of a generalendotheliitis 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.[40][41]
In 1865, theSwiss anatomistWilhelm His Sr. first coined the term "endothelium".[42] In 1958, A. S. Todd of theUniversity of St Andrews demonstrated that endothelium in human blood vessels have fibrinolytic activity.[43][44]
^Félétou, Michel (2011),"Multiple Functions of the Endothelial Cells",The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators, Morgan & Claypool Life Sciences, retrieved2024-05-20
^Griffioen, A. W.; Molema, G. (2000). "Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation".Pharmacological Reviews.52 (2):237–268.PMID10835101.
^abBouïs D, Kusumanto Y, Meijer C, Mulder NH, Hospers GA (February 2006). "A review on pro- and anti-angiogenic factors as targets of clinical intervention".Pharmacological Research.53 (2):89–103.doi:10.1016/j.phrs.2005.10.006.PMID16321545.
^Tsukahara T, Tsukahara R, Haniu H, Matsuda Y, Murakami-Murofushi K (September 2015). "Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma".Molecular and Cellular Endocrinology.412:320–329.doi:10.1016/j.mce.2015.05.021.hdl:10069/35888.PMID26007326.S2CID10454566.
^Iantorno M, Campia U, Di Daniele N, Nistico S, Forleo GB, Cardillo C, Tesauro M (April 2014). "Obesity, inflammation and endothelial dysfunction".Journal of Biological Regulators and Homeostatic Agents.28 (2):169–176.PMID25001649.
^Mäyränpää MI, Heikkilä HM, Lindstedt KA, Walls AF, Kovanen PT (November 2006). "Desquamation of human coronary artery endothelium by human mast cell proteases: implications for plaque erosion".Coronary Artery Disease.17 (7):611–621.doi:10.1097/01.mca.0000224420.67304.4d.PMID17047445.S2CID1884596.
^Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, et al. (January 2005). "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 of Hypertension.23 (1):7–17.doi:10.1097/00004872-200501000-00004.PMID15643116.
^Roberts OL, Holmes K, Müller J, Cross DA, Cross MJ (December 2009). "ERK5 and the regulation of endothelial cell function".Biochemical Society Transactions.37 (Pt 6):1254–1259.doi:10.1042/BST0371254.PMID19909257.
^*Milosevic V, Edelmann RJ, Fosse JH, Östman A, Akslen LA (2022). "Molecular Phenotypes of Endothelial Cells in Malignant Tumors.". In Akslen LA, Watnick RS (eds.).Biomarkers of the Tumor Microenvironment. Cham: Springer. pp. 31–52.doi:10.1007/978-3-030-98950-7_3.ISBN978-3-030-98949-1.
^Mohammadi-Sartang M, Bellissimo N, Totosy de Zepetnek JO, Bazyar H, Mahmoodi M, Mazloom Z (December 2018). "Effects of walnuts consumption on vascular endothelial function in humans: A systematic review and meta-analysis of randomized controlled trials".Clinical Nutrition ESPEN.28:52–58.doi:10.1016/j.clnesp.2018.07.009.PMID30390893.S2CID53221430.
^Xiao Y, Huang W, Peng C, Zhang J, Wong C, Kim JH, et al. (June 2018). "Effect of nut consumption on vascular endothelial function: A systematic review and meta-analysis of randomized controlled trials".Clinical Nutrition.37 (3):831–839.doi:10.1016/j.clnu.2017.04.011.PMID28457654.S2CID13930609.
^Félétou, Michel (2011),"Introduction",The Endothelium: Part 1: Multiple Functions of the Endothelial Cells—Focus on Endothelium-Derived Vasoactive Mediators, Morgan & Claypool Life Sciences, retrieved2024-05-20
