Endothelium is the term used to describe the innermost cellular layer of blood and lymphatic vessels. It is a single-celled layer of endothelial cells. The endothelium regulates the exchange of substances between blood and body tissues, it produces important messenger substances, and it influences the clotting ability of blood and the formation of new blood vessels (angiogenesis).
What is the endothelium?
The endothelium consists of a single-celled layer of endothelial cells that form a so-called squamous epithelium and line the inside of all blood and lymphatic vessels. The endothelium performs a variety of functions and has a decisive influence on the exchange of substances between blood and body tissue. This function is particularly important in the capillaries, where the oxygen-rich arterial blood of the large body circulation releases oxygen and takes up “used” substances and transports them away as now oxygen-poor venous blood. The surface area covered by the endothelium in the vessels is about 7,000 square meters, and the number of endothelial cells in humans reaches the impressive number of more than 10 trillion. In the vessels supplying the brain, the endothelium plays a special role in maintaining the blood-brain barrier. In the brain region, the endothelium is virtually impermeable to substances, except for selective groups of substances that can cross the endothelium with strictly specific effective transport mechanisms and thus overcome the blood-brain barrier.
Anatomy and structure
The endothelium, which lines the inside of blood and lymphatic vessels, consists of a unicellular layer of endothelial cells interconnected in the form of a squamous epithelium. Below the endothelium is the basal lamina as part of the basement membrane, which connects to the underlying tissue and is interspersed with reticular fibrils. Endothelial cells are formed by differentiation of partially potent angioblasts, which in turn develop from the multipotent stem cells of the blood and vascular system, hemangioblasts. Hemangioblasts are available for life as stem cells in the blood. Depending on the functional areas in the body, the endothelial cells are connected to each other to different degrees and thus form differently effective substance barriers. In principle, the connection between the endothelial cells consists of “tight junctions” in the form of thin strands of transmembrane proteins such as occludin. Depending on the ability to exchange substances, a distinction is made between continuous, discontinuous and fenestrated endothelium. While the continuous endothelium only allows highly selective mass transfer via specialized transport vehicles, the discontinuous endothelium has small gaps that allow mass transfer with certain substances even without transport vehicles. The fenestrated endothelium is particularly permeable to hydrophilic substances and to water.
Function and Tasks
The endothelium fulfills a number of important physiologic roles beyond its function as the inner wall lining of blood and lymphatic vessels. One of the most important tasks is to regulate the exchange of substances between the blood and surrounding body tissues. This task is particularly critical in the brain, where, to protect neurons, the continuous endothelium maintains the blood-brain barrier and allows only selective transport of substances via specific transport vehicles. Another task is the regulation of blood pressure via specific messenger substances. First and foremost are nitric oxide (NO) and prostacyclin. Both substances are synthesized by the endothelium and lead to relaxation of the smooth muscles in the vessel walls, resulting in a reduction in blood pressure via the increase in lumen in the arteries. However, the endothelium also synthesizes endothelin, which causes the smooth muscle in the vessel wall to contract, thus increasing blood pressure. The endothelium also influences the coagulation process. The clotting process can be activated or inhibited by substances synthesized by the endothelium. When required, the endothelium produces tissue plasminogen activator (tPA), which modulates the thrombus solution via the formation of plasminogen. The endothelium also plays an important role in inflammatory processes. Local activation of the endothelium attracts various types of leukocytes such as neutrophil granulocytes, monocytes, macrophages and T lymphocytes.At the appropriate site, the attracted leukocytes can be guided by a specific transport mechanism out of the blood vessel through the vessel wall into the surrounding tissue, where they can fight an infection recognized by the immune system. When the body needs new blood vessels (angiogenesis), the endothelium also assumes an important function here. The endothelium releases substances that cause new blood vessels to sprout.
Diseases
The differentiated and complex physiologic roles performed by the endothelium suggest that malfunction or dysfunction of the endothelium can have serious consequences. Inflammation, injury, or certain toxins can cause dysfunction of the endothelium, leading to secondary damage such as atherosclerosis, disruption of blood coagulation, and immune system misdirection. Endothelial dysfunctions can, for example, affect the blood pressure regulation mechanism and the permeability of the vessel walls to certain substances in a way that leads to pathological effects. Dysfunctions in endothelial regulatory mechanisms are mainly discussed as causative agents of atherosclerosis. Other authors postulate the hypothesis that only pathological changes in the vessels lead to a dysfunction of the endothelium, i.e. that the cause-effect is exactly reversed. A disturbance in nitric oxide synthesis, known as eNOS (endothelial NO synthase), has a particularly serious effect. In addition to its vasodilatory property, the messenger substance nitric oxide influences a number of other vasoprotective mechanisms of action that are of great importance for the preservation of endothelial functions. Chronic reduction in NO production may be responsible for a number of vascular diseases. An early marker of endothelial dysfunction is low levels of albumin in the urine (microalbuminuria). However, microalbuminuria may also indicate renal damage, so it is essential to make a differential diagnosis.
