It is the cellular layer that covers the blood vessels of the body, it is extremely resistant.
At a few hundred nanometers thick, this tenuous structure constantly resists blood flow, hydrostatic pressure , stretching and tissue compression to create a unique and highly dynamic barrier.
Which maintains a necessary structure which divides the tissues of the body’s circulatory system .
The endothelium is also extremely adaptable.
In cases where the barrier must be physically violated to allow immune cells to reach various regions of the body to fight infections.
The endothelium cooperates with leukocytes to create openings that provide infection-fighting cells with immediate access to their targets.
These subsequent “micro wounds” are ephemeral, as soon as the cells have crossed the endothelium, these pores and spaces heal quickly, restoring the efficient barrier function of the system.
In cases where these gaps do not close and leaks occur, the results can lead to dramatic pathologies that include sepsis , acute lung injuries and ischemic cardiovascular diseases, as well as chronic inflammatory diseases such as diabetes and arthritis .
The endothelium forms the inner cell lining of all the blood and lymph vessels in the body and is an excellent example of where biology meets physics and engineering.
It must convert mechanical forces into chemical signals to maintain homeostasis.
The endothelium is located between the blood and the vascular wall, acts as a receptor and transmitter of signals.
These endothelial cells recognize hemodynamic changes in the blood, respond to these changes through numerous vasoactive, immune and metabolic processes, by releasing numerous biologically active factors such as:
- Nitric oxide.
- Hyperpolarizing factor derived from the endothelium.
- Transforming growth factor.
- Vascular endothelial growth factor.
- Growth factor of basic fibroblasts.
- Growth factor derived from platelets.
- Tissue plasminogen activator.
- Tissue plasminogen activator inhibitor type 1.
- Reactive oxygen species.
- Monocyte adhesion molecules.
These factors intervene in the tone and growth of the vascular smooth muscle, as well as in processes such as coagulation, fibrinolysis and adhesion of blood cells to the vascular wall .
It also controls the immune response, drug administration through the vasculature and cancer metastasis .
Endothelial dysfunction is a marker of preclinical atherosclerosis characterized by altered endothelium-dependent vasodilatation and a proinflammatory state that promotes the development of atherosclerosis.
The menopause marks an increase in endothelial dysfunction.
In comparison with men, age-related endothelial dysfunction is attenuated in premenopausal, normotensive, and hypertensive women.
However, after menopause there is a strong decrease in endothelium-dependent vasodilation and by the age of 60 there are no observable sex differences.
This indicates an association between endothelial dysfunction and reduction in endogenous estrogen production .
Markers of activation and endothelial dysfunction
Endothelial activation and dysfunction are characterized by a change in the balance of vasomotor factors released by the endothelium, expression of inflammatory cytokines and chemokines, expression and secretion of selectins and adhesion molecules and modulation of local thrombotic pathways.
It has been demonstrated that the measurement of the circulating levels of markers and relevant mediators of these pathways provide important physiopathological data on the influence of the endothelium in the processes of atherosclerotic diseases.
Although limited by the fact that the systemic levels of these biomarkers may not actually represent their local levels and activity in the vascular wall.
Endothelial cell injury typically accompanies vascular inflammation.
Therefore, fragments of activated endothelium, endothelial microparticles and even entire endothelial cells are poured into the circulation.
These can be measured in the blood and their circulating levels increase in association with coronary endothelial dysfunction, unstable coronary syndromes and vasculitis .
Role in endothelial hemostasis
The main reason why blood in the vascular system remains fluid is the presence of endothelium.
Endothelium actively participates in a large number of physiological and pathological processes, is an active participant in hemostasis, works to decrease thrombosis and if damaged, promotes thrombosis through the exposure of blood to tissue factor.
This prostaglandin works to keep the vessels open (vasodilation).
It also prevents platelet aggregation by acting on platelets to increase cyclic adenosine monophosphate, which effectively reduces the amount of thromboxane A2 that has procoagulant activities.
When platelets come into contact with collagen, they produce adenosine diphosphate, which further promotes platelet aggregation.
The endothelium produces nitric oxide in response to adenosine diphosphate of activated platelets.
This nitric oxide works to maintain vasodilatation, which decreases the likelihood of coagulation.
Protein C is released from the endothelium in response to thrombin, acts to inactivate some of the coagulation factors.
A substance similar to heparin is produced on the surface of endothelial cells that acts to inactivate thrombin.
The endothelial cells act to help the dissolution of the clot, releasing plasminogen activators, this is a key molecule involved in the breakdown of clots after they have formed.
Closing of the micro wounds
The leukocytes generate ” invasive podosomes “, which produce vascular micro wounds through an endothelial perforation.
When the endothelium detects an acute loss of isometric tension, in response, as a biomechanical signal it generates reactive oxygen species, which are responsible for coordinating the process of closing the microheride.
The endothelium has an active role in closing pores and gaps made by leukocytes, endothelial cells generate structures called lamellipodia, which then migrated to the sites of the microherides to close them.