Vascular endothelial cell

= Vascular endothelial cells =

Content
Artery description Endothelial cells (endothelium, endothelium ) form a simple layer of cells lining the inside of blood vessels. They are not considered to be the right epithelium because they arise from the mesenchyme. They have an elongated polygonal shape, contain numerous pinocyte vacuoles and form complex connections with neighboring cells. They also contain Weibel-Palade bodies (0.1 × 3 µm), which store the von Willebrand factor. The structural and functional integrity of endothelial cells is a basic prerequisite for vascular wall homeostasis and blood circulation.
 * 1Endothelial function
 * 2Endothelial dysfunction
 * 3Links
 * 3.1related articles
 * 3.2Source

Endothelial function

 * The semipermeable membrane of the endothelium controls the transfer of small and large molecules to the artery wall and further through the capillary wall and venules. In most areas of the human body, intercellular junctions are normally impermeable to these molecules, but relatively unstable junctions between endothelial cells can spread due to hemodynamic factors ( blood pressure ) and vasoactive substances (eg histamine in inflammation).
 * They maintain a non-thrombogenic interface between blood and tissue, regulate thrombosis, thrombolysis and platelet adherence.
 * They modulate vascular tone and blood flow.
 * They metabolize hormones.
 * They regulate immune and inflammatory responses by acting on the interaction between the vessel wall and leukocytes.
 * They modify lipoproteins in the artery wall.
 * They also regulate the proliferation of other cells, especially vascular smooth muscle.

The vascular endothelium is a dynamic endocrine organ that regulates contractile, secretory and mitogenic activities of the vessel wall and hemostatic processes in the lumen of the vessel. In addition to involvement in the formation of blood clots ( thrombus ), endothelial damage is a key factor in the development of atherosclerosis, and indirectly hypertension , and participates in diseases of many other organs.

The endothelium produces vasoactive substances in response to changes in blood flow, oxygen tension, and various other stimuli through receptors. Endothelium-dependent vascular dilatation is mainly realized by the nitric oxide radical NO · (formerly referred to as EDRF = endothelium-derived relaxing factor), to a lesser extent by prostacyclin and hyperpolarization factor, which is an activator of ATP- and Ca 2+ -dependent K + -ionic channel. Endothelial vasoconstrictors include endothelin-1 (ET-1) and thromboxane A 2. The balance between the two adverse substances in both physiological and pathological situations determines the contractile and probably mitogenic state of the smooth muscle of the respective vessel. NO · is synthesized in various cell types by the conversion of L-arginine to L-citrulline catalyzed by NO-synthase (NOS). 3 isoforms of NOS were identified.

See the NO-synthase page for more information .

Endothelial dysfunction
Endothelial dysfunction leads to impaired vascular relaxation, promotes platelet aggregation, increases vascular smooth muscle proliferation and leukocyte adhesion to the endothelial cell surface. Surface adhesion molecules are expressed, facilitating the capture of circulating leukocytes. Leukocyte adhesion together with smooth muscle proliferation are key moments in the development of atherosclerotic plaques. The state of mechanical integrity of the plaque determines the clinical manifestation of atherosclerosis. Rupture of the plaque with subsequent thrombus formation is the cause of most sudden coronary events. A stable atheroma plaque usually has a solid fibrous envelope, a smaller lipoid nucleus, and fewer infiltrated leukocytes than a plaque that has ruptured. Inflammation mediators such as cytokines, oxidized LDL and infectious agents ( cytomegalovirus, Chlamydia pneumoniae) may weaken the integrity of the fibrous envelope. Thus, endothelial dysfunction is not only an early marker of atherosclerosis, but also contributes significantly to the development of atherogenesis.

Neuronal and endothelial NOS consistently produce small amounts of NO ·, while persistently large amounts of NO · are produced by macrophage NOS or NOS from smooth muscle cells upon induction of certain cytokines. Vessels affected by atherosclerosis suffer from endothelial dysfunction, as evidenced by impaired vasomotor function for loss of NO • action, which has antiatherogenic and anti-inflammatory effects. Superoxide anion also leads to inactivation of endothelial NO ·, causing vasoconstriction and hypertension. Endothelial dysfunction is also attributed to abnormal or excessive release of vasoconstrictors such as endothelin-1 (its plasma concentration is increased in patients with advanced atherosclerosis and acute coronary syndrome). Oxidative stress leads to the oxidation of LDL particles, which then inhibit NOS. Macrophages and smooth muscle cells are the main sources of reactive oxygen species in atherosclerotic vessels. The final effect depends on the balance of interactions between antioxidants and oxidants. Oxidative stress is involved in the atherogenic process by inducing pro-inflammatory mediators :

Activation of the proinflammatory transcription factor (nuclear kappa B (NF-κB) or activator protein-1 (AP-1) and early growth response factor - egr-1) is caused by the action of hydrogen peroxide formed during the oxidation cascade. Adhesive molecules such as VCAM-1, ICAM-1 and E-selectin, numerous cytokines, growth factors such as M-CSF contain functional DNA-binding sequences for NF-κB, AP-1 and egr-1, the expression of which is induced by these transcription factors. NF-κB activation is inhibited by antioxidants and anti-inflammatory drugs such as salicylates or corticoids. Atherosclerosis is considered a chronic inflammatory process initiated and exacerbated by oxidative stress. Thus, antioxidants prevent the development of atherosclerosis by inhibiting the activation of proinflammatory transcription factors that are required for the expression of cellular adhesion molecules, cytokines, and growth factors in the vessel wall.

The nitric oxide radical formed in the endothelial cell inhibits the expression of cellular adhesive molecules on the endothelial surface and thus prevents the adhesion of leukocytes to the vessel wall. This is done by inhibiting the proinflammatory transcription factor NF-κB (expression of proinflammatory cytokines, adhesion molecules and growth factors depends on their transcriptional induction by NF-κB).

Reduction of vasodilation induced by reduction of endothelial NO · contributes to myocardial perfusion disorders ; oxidative stress inhibits NO-synthase by oxidizing the peroxynitrite formed from the superoxide anion by its key cofactor - tetrahydropterin. The formation of reactive oxygen species and nitrogen in endothelium has been shown to affect xanthine oxidase activity; administration of its inhibitor - allopurinol - may therefore help to prevent myocardial damage in chronic heart failure.

Links
https://www.wikiskripta.eu/index.php?curid=30569

Related Articles

 * Atherosclerosis

Source

 * MASOPUST, Jaroslav, et al. Cell pathobiochemistry. 1st edition. Prague: Charles University, 2nd Faculty of Medicine, 2003. 344 pp. 88–92.  ISBN 80-239-1011-6.