Endothelial cell

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An endothelial cell is the type of flat cell that lines the inside of all blood vessels (including capillaries), and is in permanent contact with the blood. They are about 25 to 50 micrometers (μm) long and 10 to 15 μm wide. They act as regulators of cellular and molecular traffic from the blood into the tissues. They have a highly differentiated and specialized structure with two types of junctions between cells: some are tight (tigh) and others are weak (gap). The endothelial cell synthesizes and releases vasoactive substances that regulate vascular tone, blood pressure, and local blood flow; also substances that participate in coagulation, in fibrinolysis and in inflammatory and immunological reactions.

Endothelial cell morphology

In the endothelial cell there is great heterogeneity at the level of its morphology, function, gene expression and antigenic composition.
The regulation of this endothelial heterogeneity is given by environmental signals, metabolism, cell-matrix interactions, cell-cell interactions, and the typical growth factors of each organ.
Endothelial phenotypes vary between different organs, between different segments of the vascular bed of the same organ, and between neighboring cells of the same organ.

Microarchitecture

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Human endothelials. Immunohistochemicals to demonstrate the surface membrane (green) and intercellular interdigitations (to the center). Confocal microscope.

Cells of the endothelium are approximately 25-50 micrometers (μm) long and 10-15 μm wide. Its major axis is arranged parallel to the direction of blood flow.
Endothelial cell borders are irregular, neighboring cells show interdigitations and have intersecting serrated areas.
Each endothelial cell is shaped like a thin, curved plate, polygonal in profile, with a central thickness of 3-4 μm and approximately 0.1-0.4 μm at the edges.

Nucles (in negative) within immune endothelial cells for tubulin α.

The cell nucleus is very flattened and therefore appears elliptical in histological sections. The nuclear region is the thickest in the cell and bulges out in the lumen. The thinnest, peripheral portion of the cell is extremely thin, and the cell membranes facing the light or tissue are separated by a layer of cytoplasm 0.2-0.4 microns thick.

In the region near the nucleus, a Golgi complex and a few mitochondria are found, while in the peripheral thin region of the cytoplasm are tortuous tubular elements of the endoplasmic reticulum. Lysosomes are rare, but multivesicular bodies are not uncommon.

Ultrastructure

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3D human endothelials are observed digits. Red blood cells (arrow marks). Electronic sweep microscope.

The luminal surface of cells is normally smooth in profile, but often the edges of neighboring cells may overlap and a ridge or tab may then project into the lumen for a short distance.

Endothelial cells show two types of junctions, tight junctions and weaker junctions (gap junction). These tight junctions have the ability to limit the transport of substances and molecules, and act as a mechanical barrier.

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Nucles of two endothelial cells. Close unions up and down. Numerous vesicular bodies. E= erythrocyte inside vascular light.
Zonula occludens (tight) of an endothelial cell. Criofracture with electronic sweeping microscope.

The junctions between endothelial cells must be capable of reacting and modifying their composition in certain situations, but at the same time they must be stable structures capable of resisting the blood flow to which they are continuously subjected.

Their response to different stimuli must be controlled in intensity, but also in time, since a sustained increase in permeability can trigger a process of chronic inflammation. In this way, the endothelium fulfills an essential barrier function for vascular homeostasis. They are sensitive to changes in flow pressure, inflammatory signals, and circulating hormones.

A striking feature of endothelial cells is the presence of a large population of plasmalemma vesicles about 70 nanometers (nm) in diameter, slender-necked, which are present on both cell surfaces and open to the light and to the extravascular space.

Weibel-Palade bodies are structures with a diameter of 0.1-0.3 (μm) and a length of 1-5 μm.

Weibel-Palade Corps, Ultrastructure.

In cross section, they consist of electron-dense tubules with an inner diameter of 12 nm, surrounded by a less dense matrix and packed into parallel bundles that are surrounded by a lipid bilayer. It is where two major molecules, von Willebrand factor and P-selectin, are manufactured, stored, and released. They are bound at the periphery of the cell to the actin cortex and serve as an easy-release pool.

On the extraluminal or external surface, endothelial cells are in contact with the basement membrane and substances such as collagen, proteglycans, heparansulfate, integrins; in the luminal part, endothelial cells in contact with blood have mucopolysaccharides, glycoproteins, fibrinogen, and some fibrin.

Functions of endothelial cells

Endothelial cells (EC) form the single-layered vascular endothelium, which lines the inside of blood vessels, separating the tissues from the blood.
In the adult human body, the aggregate of the entire vascular endothelium can weigh as much as 1 kilogram and in the microcirculation comprises an area of 1-7 square meters (m2). for some and between 500-700 m2 for others.

Exocytosis: vesicles and exosomes.

EC act as regulators of the traffic of cells and molecules from the blood to the interior of the tissues, thanks to their differentiated and specialized structure.
These cells have several roles in homeostasis, including the following:

  1. They form a smooth surface that facilitates the laminar flow of the blood and prevents the adherence of the blood cells.
  2. They form a barrier of permeability for the exchange of nutrients between plasma and cell intersection, while regulating the transport of substances between them.
  3. They regulate angiogenesis and vascular remodeling.
  4. They contribute to the formation and maintenance of the extracellular matrix.
  5. They produce growth factors in response to vascular damage, especially influencing vascular smooth muscle proliferation.
  6. They produce substances that regulate platelet aggregation, coagulation and fibrinolysis.
  7. They synthesize and degrade various hormones.
  8. They participate in the immune response by generating cytokines that modulate the activity of lymphocytes.
  9. They release agents that act parachrine over adjacent smooth muscle cells, regulating their contraction. Vascular endothelium produces and releases vasodilating substances and vasoconstrictors. Among the vasodilators are: nitric oxide (NO) (formerly known as a relaxing factor derived from endothelium or EDRF), hyperpolarizing factor derived from endothelium (EDHF) and prostacycline. Among the vasoconstrictive substances are: endothels and tromboxane A2.

Endothelial cell turnover

In adults, endothelial cells are inactive, that is, they are not growing cells (proliferating).
They constantly go through cycles of regeneration and programmed cell death (apoptosis), every 3 months all the endothelial cells are renewed. The half-life of a normal endothelial cell in the heart is approximately 6 years. In the liver and spleen, about 1% of all endothelial cells proliferate in the quiescent state.
This resting state in endothelial cells is defined by minimal or absent endothelial cell proliferation and migration, minimal vascular leakage across the endothelial barrier, and minimal expression of leukocyte adhesion molecules.
The "inactive" is fully "awake" as it receives and initiates input signals, which are important to its function. These "dormant" they do a lot of active work, such as secreting paracrine and endocrine factors, and maintaining the barrier to cell survival. Endothelial cells "inactive" they require active maintenance to preserve normality in a manner that is tissue-specific.
Microenvironmental stimuli (such as shear stress, hypoxia, and specific growth factors) and epigenetics continually define and optimize the local characteristics of endothelial cells.

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