Research Area

Vascular Endothelium


Introduction of vascular endothelium

Vascular endothelial cells are a layer of monocytes between the bloodstream and the vascular wall tissue. They can secrete a series of NO, PGI2, ET-1 and other vasoactive substances through autocrine, endocrine and paracrine pathways to regulate the tension of blood vessels, antithrombotic, inhibition of smooth muscle cell proliferation and vascular wall inflammation and other functions. NO is the most important vasodilator factor produced by endothelial cells. It is produced by the endothelial cell NO synthase (eNOs) acting on L-arginine. NO can diffuse to the smooth muscle cells of the vascular wall to activate ornithine cyclase, which regulates vasodilation by cGMP. In addition, NO also has the effect of inhibiting platelet aggregation, inhibiting adhesion of monocytes to endothelial cells, and inhibiting proliferation of smooth muscle cells. However, when the vascular endothelium is subjected to a series of harmful factors, the vasodilators released by the endothelial cells are reduced, the vasoconstrictors are increased, and the vascular homeostasis is broken, eventually leading to a series of cardiovascular events.

Vascular Endothelium

The function of vascular endothelium

Participation in angiogenesis

The formation of functional vascular networks requires coordination and signaling between different types of cells. Vascular endothelial growth factor provides an example of a vascular endothelial-specific growth factor. According to the angiogenesis model of the recent vascular-specific growth factor, vascular endothelial growth factor is the most critical driver of angiogenesis since angiogenesis requires the formation of immature blood vessels by angiogenesis or budding. Angiopoietin 1 and ephrinB2 are substances required for subsequent further vascular remodeling and maturation, particularly the binding of endothelial cells to supporting cells, such as smooth muscle cells and outer membrane cells. Angiopoietin 1 plays an important role in maintaining the resting state and stability of mature blood vessels

Barrier function

The vascular endothelium is a continuous cell monolayer formed by different types of adhesion structures or cell-cell junctions. These complex structures are composed of a transmembrane adhesion molecule linked to a network of cytoplasmic/cytoskeletal proteins. According to the morphological and functional characteristics, connections between endothelial cells are divided into three types: the tight junction, adhesive junction, and gap junction. The inner surface of the endothelium has a large surface area for the exchange of substances between blood and tissue. Adhesion is involved in the regulation of vascular wall permeability in circulating cells. Changing in permeability of vascular endothelium is related to redistribution of cadherin on the endothelial surface, stability of local adhesion and activation of matrix metal proteases. Loss of vascular endothelial barrier will lead to extracellular edema. Histamine, atrial natriuretic factor, and thrombin induce rapid and short-term increases in vascular permeability. Other cytokines and vascular endothelial growth factors induce longer-lasting responses.

Regulate angiotasis

Endothelial cells regulate the relaxation and contraction of blood vessels by releasing vasoactive substances such as nitric oxide (NO), prostaglandins, and vasoconstrictors such as thromboxane A2 and endothelin. Under physiological conditions, there is a balance between the two. Once the endothelial cells are damaged or the endothelial dysfunction is unbalanced, it will lead to certain diseases. Under physiological conditions, endothelial cells can produce NO, acetylcholine, angiotensin II, bradykinin, histamine, and arachidonic acid can increase NO production in endothelial cells. In addition, the release of NO is also regulated by shear stress. The three isomers of NO can be structurally expressed in the endothelium of the corresponding site. NO is not only a product of the release of the endothelium after stimulation, but also plays an important role in maintaining the vascular base tension.

Anticoagulation promotes fibrinolysis

Under physiological conditions, endothelial cells mainly exhibit anticoagulant and fibrinolysis activity, while in pathological conditions such as trauma, infection and shock, the main manifestations are enhanced procoagulant activity and decreased fibrinolysis activity. Since endothelial cells are capable of producing many important molecules that regulate blood clotting and platelet function, the normal endothelium surface has anticoagulant and antithrombotic effects. After vascular injury or stimulation by certain cytokines, endothelial cells turn to a procoagulant/thrombogenic phenotype. In bloodstream, the main anti-platelet substances are prostacyclin (PGI2) and NO. The two synergistically increase the platelet cAMP content and thus prevent platelet accumulation. According to previous studies, PGI2 and NO are structurally expressed in endothelial cells, and they take part in the process of the synthesis of molecules which involved in the blood coagulation process such as bradykinin and thrombin. At rest, endothelial cells maintain blood flow by promoting many anticoagulant pathways, most importantly the protein C/protein S pathway. Thrombin interacts with thrombomodulin to initiate the protein C/protein S pathway, which activates protein C to inactivate the essential factors VIIIa and Va. The formation of thrombin and thrombomodulin complex also prevents thrombin from agglutinating fibrinogen and platelet activation. In addition, endothelial cells are also important sites for the synthesis of tissue factor pathway inhibitors. Endothelial cells can also be involved in fibrinolysis by releasing tissue-type plasminogen activator and urokinase that promote the conversion of plasminogen to plasmin. Plasmin dissolves the thrombus by digesting the fibrin network. Tissue plasminogen activator has a basal level expressed in endothelial cells, whereas urokinase is only activated by endothelial cells.

Involved in inflammatory response

Endothelial cells interact with inflammatory cells to regulate the body's inflammatory response. Although many mediators are involved in the regulation of different stages of inflammation, white blood cells and endothelial cells are the main players in the inflammatory response. Endothelial cells dominate inflammatory cells to aggregate tissue damage and infection sites, and release cytokines and growth factors that are used to communicate signals with leukocytes. In addition, the surface of endothelial cells also expresses many important molecules regulating the leukocyte migration out of the endothelium, such as PECAM-1, CD99, VE-Cadherin and so on.

Moreover, in addition to heterogeneity in size and morphology, nuclear location, thickness, microvilli, microfilaments, vesicles and junctions, the heterogeneity of vascular endothelium includes expression levels, protein levels, gene levels, transcriptional networks, and signal transduction. This means that vascular endothelium have a complex functions.

Clinical significance

Vascular endothelium maintains the homeostasis of the vascular system by diastolic and contractile, inhibiting growth and promoting growth, antithrombotic and promotes the blood clots, anti-inflammatory and pro-inflammatory, and balanced regulation of antioxidant and pro-oxidative effects. Since the vascular endothelium is most sensitive to changes in blood components and blood flow, many factors and diseases such as smoking, hypertension, hyperlipidemia, diabetes, and heart failure can cause endothelial dysfunction; on the other hand, endothelial dysfunction can also cause many disease. A striking feature of vascular disease is the focal distribution of lesions. Recognizing the heterogeneity of vascular endothelial function, we not only select site-specific vascular endothelial markers in the study of vascular diseases, but also contribute to the establishment of a site-specific evaluation system for vascular endothelial function, to further better understand the pathogenesis and clinical manifestations of specific vascular diseases. With the deepening of vascular endothelial function research, it will provide a strong basis for the development of vascular endothelial protection and anti-angiogenic drugs.

References:

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  2. Baldwin AL, Thurston G. Mechanics of endothelial cell architecture and vascular permeability. Crit Rev Biomed Eng. 2001, 29: 247-278.
  3. Alexander JS, Elrod JW. Extracellular matrix, junctional integrity, and matrix metalloproteinase interactions in endothelial permeability regulation. J Anat. 2002, 200: 561-574.
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