By Devanssh Mehta for Prittle Prattle News
Endothelium Dysfunction and Importance of Transforming Growth (Introduction) : Molecular pathways play significant role in maintaining homeostasis and balance in the body. There are various mechanisms at molecular level which help in maintaining balance in vascular system of the body (Wilson SH and Lerman A. (2001). Vascular endothelium dysfunction is a disease where there is imbalance of vasodilation and vasoconstriction in the body and hence disrupting the endothelium in the body resulting in wide varieties of pathophysiological events, resulting in wide range of diseases (Durand MJ, Gutterman DD. (2013). Diseases such as obesity, chest pain, myocardial infarction, heart failure or heart attack are all related pathological diseases associated with vascular endothelium dysfunction (Douglas B Cines, Eleanor S Pollak, Clayton A Buck, et al. (1998).
Before going into deep understanding of this pathological event, let us understand, what is an Endothelium? Endothelium is tight cell to cell junction and membrane which separates the tissue and muscular system from the blood stream in the body (Patel JC. (2001). It is because of its nature that it acts as a barrier between the blood and the tissue system. It is permeable to certain substances and non-permeable to others. In other words it is mainly a barrier. It is also involved in various roles related to body’s reaction to various events (Verhamme P, Hoylaerts MF. (2006). Endothelium plays an important role in cardiovascular homeostasis, platelet aggregation on the walls of blood vessels, coagulation, inflammatory responses, and mainly either vasodilation of vessels or vasoconstriction of vessels (Atherton A, Born GV. (1972).
What is a Vascular Endothelium dysfunction? Let’s understand this before going further deep. Well it is a condition in which the endothelium loses its control over the balance or homeostasis in vascular system of the body. It has wide variety of pathological events related to it depending upon the site of activity in the body (Cerletti C, Evangelista V, de Gaetano G. (1999). Like if vascular endothelium dysfunction is occurring in the cardiac vessels it results in damaging vasoconstriction, leading to chest pain. Mainly vascular endothelium dysfunction results in wide variety of diseases related to blood vessels in the body without blocking of the blood vessels itself. Means it’s a non-blockage dependent reason for wide variety of pathological and cardiovascular events. It results in high rate of vasoconstriction without blocking the blood vessels due to aggregation of platelets or thrombosis. If such events happen in the large blood vessels of cardiac events, it results in acute or chronic chest pains. One important understanding regarding the vascular endothelium dysfunction is that, this pathological event has been observed to occur in more women as compared to males. Wide variety of reasons have been investigated which results in the occurrence and pathogenesis of vascular endothelium dysfunction. Such as, Smoking, Stress, Mental tension, imbalance of the periods in women, and other reasons etc.
It has been observed that Vascular Endothelium Dysfunction is the main reason for wide variety of human diseases. Like Insulin resistance, Kidney disturbances, heart attack, Stroke, Diabetes, Chronic Kidney Failure, and several viral infectious related diseases. Endothelium is mainly a cell to cell tight complex membranous barrier in the human body (Stern DM, et al. (1991).
It was once thought as the membrane which acts as a barrier between tissue and blood vessels having water and electrolytes. Further studies, on it was taken into consideration looking at its significance, and was found out to be a major role playing part of the whole vascular tree in the body. It was also known as once a “cellophane wrapper”.
During advanced studies since 1980’s, it has now have been understood to play vital role in cardiovascular system related pathophysiological events. It plays wide and vital role in maintaining the homeostasis in the whole body as both effector and sensory capabilities. It plays a vital role in blood flow across the body. Hence, any pathological event related to the flow of blood throughout the body has its pathogenesis related to the endothelium. And the disease of endothelium, which is Endothelium Dysfunction or in other words, Vascular Endothelium Dysfunction, is main reason for various damaging events in the body related to the blood flow across the body.
Role of Endothelium in the body
- Thrombolysis and thrombosis
- Coagulant mechanisms
- Leukocyte and platelet interaction
- Regulation of vascular tone and relative growth
- Angiogenesis and Cell proliferation
- Thrombolysis and thrombosis
Endothelium cells or the endothelial cells are involved in maintaining the homeostasis upon internal or external disturbances. Such as an injury or any pathophysiological change which disturbs the normal homeostasis in the body. If however, Endothelium dysfunction occurs which disrupts the the endothelium system, it results into wide variety of pathological events, and here thrombosis. So, an important thing to understand is that Endothelium dysfunction results into thrombosis, and results in symptoms in the body related to thrombosis. Hence, proper medications such as nitrates, should be used in order to treat endothelium dysfunction, because if it occurs it will lead to thrombosis.
- Coagulation mechanisms
Coagulation is in simple sense blockage of vessels, due to coagulation factors. Endothelium plays a vital role in binding of anticoagulant factors with its receptors thus maintaining blood flow homeostasis. This mechanism has been understood so far. So when Endothelium dysfunction results in it disrupts the homeostasis of binding of anticoagulant to its receptors resulting in coagulation within the blood vessels and resultant disruption to a balanced blood flow within the blood vessels.
- Leukocyte and Platelet Interaction
The relationship of leukocyte and platelet interaction with the endothelium was observed and studied around 160 years back, since then many decades after, its relevance has been understood, where endothelial cells play vital role in rolling of platelet-leukocyte interaction upon external stimuli such as mechanical injury, or mechanical stress. Leukocyte and Platelet Interaction occurs at the walls of endothelium and results in inflammatory responses, along with relative series of cascades, leading to pain and inflammation in the region where any sort of stimuli disrupts, the normal homeostasis of endothelium and endothelial cells.
- Regulation of vascular tone and relative growth
Endothelium and endothelial cells are source of various vasodialation and vasoconstriction moieties, which results in relative vasodilation or vasoconstriction based on mediators released by the endothelial cells. Dysfunction of Endothelium system or vascular endothelium dysfunction disrupts the homeostasis of release of mediators resulting in balanced vasodilation and balanced vasoconstriction, leading to various series of cardiovascular events, such as heart attack or hypertension.
- Angiogenesis and cell proliferation
It has been realized that endothelial cells and endothelium system results in formation of blood vessels in the body. They are also involved in development of cell proliferation and new blood vessels across the body. During Vascular Endothelium dysfunction the homeostasis of balance of newer blood vessels formation results in disruption of whole vascular system, resulting in related pathophysiological changes and diseases in the body.
Importance of Transforming Growth Factor β (TGF β) and its role in the body
In human body, there are various factors, which control and run the body in a balanced manner. For body to work normally, various factors play a major and important role in order to maintain balance in the whole body. Lots of growth regulators, and growth suppressors, play vital role in normal day to day homeostasis and running the human body in better manner. One such important factor is TGF β, in other words the transforming growth factor β. TGF β is important multiplayer growth factor in human body, whose disruption leads to the development, of various diseases in the whole human body. It is the growth factor which results in normal growth of vasculature of whole body. It is one of the vital growth factors which results in formation of new blood vessels and repairing the damaged blood vessels upon any external stress, such as mechanical injury to the blood vessels.
TGF β is important growth factor which plays multiple role in our body. Regarding endothelium, it helps in the growth of the endothelial cells along with various mediators, and also helps in balanced functioning of vascular endothelium system.
Upon disruption of this vital growth factor, the homeostasis in the vasculature gets disrupts and leads to various pathological events, such as Endothelium Dysfunction. And as described above, disruption of endothelium system results in various diseases such cardiovascular diseases, stroke, diabetes, insulin resistance, and many more.
The importance of mentioning TGF β in Endothelium Dysfunction is for reason as it can be drug target for the scientists who would like to develop proper treatment for endothelium dysfunction. Here, we can see that if we introduce a molecule in body which helps in disruption of proliferation and development of TGF β in the body, it can help in proper treatment of endothelium dysfunction and treatment of its effects such as cardiovascular diseases, diabetes, stroke, insulin resistance to name aa few.
TGF β plays vital role in whole vasculature system and its importance for the same has been widely studied and understood.
Hence, relevance of transforming growth factor β with relevance to Endothelium Dysfunction is an important part of our study (Michiels C. (2003).
Literature Review
- Feng W, et al. studied the role Transforming growth factor β which mediates endothelium dysfunction in rats upon high salt intake. In the experiment the researcher studied the impact of high salt intake and its relationship with mediation of tgf β related to endothelium dysfunction. From the experiment, it was completely understood, that how high salt intake results in Endothelium Dysfunction and related diseases such as Cardiovascular diseases, Diabetes and Stroke. It is an important study which helps all of us in understanding the role of high salt intake in various diseases, and especially Endothelium Dysfunction (Feng W, Ying W-Z, Aaron KJ, Sanders PW (2015).
- Walshe, et al. studied the effect of shear stress in modulation of TGF β and relative function in Endothelium.From the experiment, it was completely understood the role TGF β in normal homeostasis of the whole vasculature in the body (Walshe TE, et al. 2011).
- Schlecht, A. et al. studied the role played by proliferation of TGF β in vision loss in experimental animals. From the study the researcher completely understood the role played by the Transforming growth factor in the pathogenesis of vision loss associated with the Endothelium dysfunction. Hence, the study done by the researcher is an important study which helps us in understanding the endothelium dysfunction disease and its effects at the molecular level in the whole body (Schlecht A, et al. (2017).
- Misaki Yamashita, studied the Inhibition of transforming growth factor beta signaling pathway promotes differentiation of human induced pluripotent stem cell‑derived brain microvascular endothelial‑like cells. It is a relevant study.
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