Endothelium Dysfunction and Role of Tumour Necrosis

By Devanssh Mehta for Prittle Prattle News

Factor-Alpha in Endothelium Dysfunction

Endothelium Dysfunction is a condition in which the Endothelium adverse effects are seen and there is disruption of balanced homeostasis due to Endothelium on vascular tree leading to severe vasoconstriction due to increased presence of vasoconstrictive autacoids (F. Ribeiro, et al. (2009).. Various diseased condition and pathological conditions are responsible for Endothelium Dysfunction such as Smoking, Obesity, and Cardiovascular Diseases and cardiovascular events. Depending on the site of vascular tree, the disruption of function of Endothelium shows respective effects. Like in large vessels of heart if endothelium dysfunction is observed it leads to high chest pain condition which is mainly a non-blockage of vessels chest pain condition (R. G. Dias, et al. 2011). As of now various markers in form of progenitor cells can be used in order to detect Endothelium Dysfunction in the body or at the site of pathophysiological conditions. 

Endothelium Dysfunction is mainly a condition where there is imbalance in vasodilation and vasoconstriction actions of Endothelium itself. In Endothelium Dysfunction more of Vasoconstriction is observed due to increased presence of vasoconstrictive autacoids at the site of pathophysiological event (R. J. Gryglewski (2008).

It has been widely studied and understood the role of Endothelium in maintaining the homeostasis of whole vascular system in the body. It releases various molecules which perform either vasodilation or vasoconstriction on blood vessels in the body. Endothelium is basically a barrier between the blood and tissue and smooth muscle system in the whole body. Endothelium releases various molecules such as, Nitric oxide, agents increasing secretion of NO, agents responsible s anticoagulants, anti-adhesion agents, agents decreasing the molecules responsible for increased NO degradation inside the vascular system of the body. Upon Endothelium Dysfunction all these actions becomes opposite and there happens decreased secretion or level of Nitric oxide in the body, increased coagulation of blood vessels in the body, increased degradation of nitric oxide in the body. From the study of Endothelium Dysfunction it has been observed and studied the importance of Nitric Oxide in the body. Nitric oxide is highly important for the maintenance of homeostasis of the whole vascular tree in the body. Even Anticoagulant autacoids are also important agents responsible for balanced homeostasis in the whole body. They maintain free flow of blood in the vascular system of the whole body, and helps in avoiding coagulation at the site of injury or mascular stress, and reverses the coagulation of blood in order to bring back the homeostasis in the body (L. Grbović, M. (2001).

It has been observed that various diseases affects the endothelium and cause endothelium dysfunction in the body. Diseases such as Cardiovascular diseases, Diabetes, Smoking, Stress, Insulin resistance, etc. cause more or severe condition of Endothelium Dysfunction in the body. Important thing to be understood is that it is non-obstructive condition of vascular system leading to higher rate of vasoconstriction due to increased express of vasoconstrictive autacoids inside the vascular system of the body (M. Radenković, et al. (2012).

Endothelium Dysfunction can be reversed by using various drugs used for cardiovascular diseases, and role mainly the statins has been observed significantly in reversing the diseased condition of Endothelium Dysfunction in the body (Y. Hirata, et al. (2010)

Role of Tumour Necrosis Factor-Alpha in Endothelium Dysfunction

TNF-α is pro-inhibitory cytokine which has been studied widely responsible for the pathogenesis of Endothelium Dysfunction. It has been observed that TNF-α receptor 1 and TNF-α receptor 2, where majorly TNF-α receptor 1 is responsible for major expression of TNF-α induced Endothelium Dysfunction. TNF-α causes Endothelium dysfunction by decreasing the levels of Nitric oxide in the vascular system along with increased degradation of Nitric oxide with inducing oxidative stress in the whole body (Picchi et al. (2006).  It has been observed and widely studied that TNF-α is mainly responsible for increasing Free radicle generation in the body and also increasing the inflammatory responses across the whole vascular infrastructure of the body. Various research’s have been carried out where it has been observed and tested the role of TNF-α in increasing the pathophysiological reason for Endothelium Dysfunction. As has been already written that in Endothelium Dysfunction there is mainly imbalance of vasodilation and vasoconstriction in the vascular structure of the body, the TNF-α here leads to increasing the risk factors associated with the Endothelium Dysfunction and also increasing the other pathophysiological events responsible for the over expression of stress, oxidative stress, inflammatory responses, damage to the anticoagulation and coagulation balance in the body and damage to the increased expression of Nitric oxide in the body. It has been observed and widely tested that TNF-α leads to increased vasoconstrictive autacoids expression in the body leading to over expression of Endothelium Dysfunction along with its associated pharmacological as well as pathophysiological events in the whole vascular infrastructure of the body. Not only this it has been also widely studied and observed that TNF-α leads to increased neurodegenerative processes in the body, also increasing the risks of causing cancer in the whole body (Iwasima, T, et al. 2019). Ever since the importance of TNF-α has been discovered in the pathophysiology of wide variety of diseases, it has been widely studied and its relationship has been understood in relation to not only Endothelium Dysfunction, but also Neuro-Degenerative diseases, Nervous system disorder, Obesity, Diabetes, Insulin resistance, Inflammatory responses across the body and increased expression of cancer at various sites in and around the whole body (Gao, X. et al. 2007).  TNF-α is mainly involved in the homeostasis of various systems in the body. And on its over expression due to mechanical stresss or internal and external factors it leads to imbalance cascade of reactions across the body. This is mainly responsible for the expression of wide variety of diseases in various systems of the body and leading to plethora of diseases to the human body. There it has been selected for the purpose of study, as TNF-α is very important cytokine to be studied and its role in the pathogenesis of various diseases. 

TNF-α increases the risks factors associated with factors responsible for the occurrence of Endothelium Dysfunction in the body, as it leads to high rate of vasoconstriction by increasing the oxidative stress, and decreasing the expression of Nitric oxide in the vascular infrastructure of the body. Thus it has been observed that TNF-α plays a degenerative role in the pathophysiology of Endothelium Dysfunction (Gao, X. et al. 2008).

Literature Review

1. (Picchi, A. et al. 2006) studied the overexpression of TNF-α in the pathophysiology of Endothelium Dysfunction in Zucker observed Diabetic rats. The ZOB rats were tested by injecting various chemicals including TNF-α agent and were tested using vararious markers for testing the role TNF-α in the pathophysiology of Endothelium Dysfunction. From the study by the researcher, it was confirmed that TNF-α plays a significant role in increasing the risks factors associated for causing Endothelium Dysfunction in the body.
2. (Iwasima, T, et al. 2019) studied the attenuation activity of the plant Aronia meranocalpa in the TNF-α induced human endothelial cell lines. From the experiment, it was observed that the Aronia berry the plant increased the attenuation of cytokines induced inflammatory responses in the body. And it has also been observed that the plant Aronia berry helps in attenuation of TNF-α induced Endothelium Dysfunction in the body. 
3. (Gao, X. et al. 2008) studied the role played by TNF – α in increasing the oxidative stress in the body leading to the causation of endothelium dysfunction in the body. From the experiment carried out by the researcher, it was clearly observed that chemicals which were responsible for decreased expression of TNF-α in the body helped in lowering the risk factor associated with Endothelium Dysfunction. 
4. (Gao, X. et al. 2007) studied whether TNF-α increases the risks of causing Endothelium Dysfunction via increasing oxidative stress. From the experiment carried out by the researcher it was clearly observed that TNF-α plays significant role in increasing the risks of causing Endothelium Dysfunction via increasing the oxygen free radicals in the vascular infrastructure of the body. 

References

1. F. Ribeiro, A. J. Alves, M. Teixeira, V. Ribeiro, J. A. Duarte, and J. Oliveira (2009). “Endothelial function and atherosclerosis: circulatory markers with clinical usefulness,” Revista Portuguesa de Cardiologia, vol. 28, no. 10, pp. 1121–1151.

2. R. G. Dias, C. E. Negrão, and M. H. Krieger (2011). “Nitric oxide and the cardiovascular system: cell activation, vascular reactivity and genetic variant,” Arquivos Brasileiros de Cardiologia, vol. 96, no. 1, pp. 68–75.

3. R. J. Gryglewski (2008). “Prostacyclin among prostanoids,” Pharmacological Reports, vol. 60, no. 1, pp. 3–11.

4. M. Radenković (2012). “Endothelium-derived hyperpolarizing factor and pregnancy: possible contribution in regulation of vascular signaling mechanisms in normotensive and hypertensive settings,” in Pregnancy: Risk Factors, Management and Recovery, T. Altamirano Frias and M. J. Cano, Eds., pp. 205–220, NOVA Publishers, New York, NY, USA.

5. L. Grbović, M. Radenković, M. Prostran, and S. Pešić (2001). “Characterization of adenosine action in isolated rat renal artery. Possible role of adenosine A(2A) receptors,” General Pharmacology, vol. 35, no. 1, pp. 29–36.

6. M. Radenković, M. Stojanović, R. Janković, M. Topalović, and M. Stojiljković(2012). “Combined contribution of endothelial relaxing autacoides in the rat femoral artery response to CPCA: anadenosine A2 receptor agonist,” 􀄇e Scienti􀄕c World Journal, vol. 2012, Article ID 143818, 7 pages.

7. M. Radenković, L. Grbović, N. Radunović, and P. Momčilov (2007). “Pharmacological evaluation of bradykinin effect on human umbilical artery in normal, hypertensive and diabetic pregnancy,” Pharmacological Reports, vol. 59, no. 1, pp. 64–73.

8. M. Radenković, M. Stojanović, and M. Topalović (2010).“Contribution of thromboxane A2 in rat common carotid artery response to serotonin,” Scientia Pharmaceutica, vol. 78, no. 3, pp. 435–443, 2010.

9. Y. Hirata, D. Nagata, E. Suzuki, H. Nishimatsu, J. I. Suzuki, and R. Nagai(2010). “Diagnosis and treatment of endothelial dysfunction in cardiovascular disease: a review,” International Heart Journal, vol. 51, no. 1, pp. 1–6.

10. D. Versari, E. Daghini, A. Virdis, L. Ghiadoni, and S. Taddei (2009). “Endothelium-dependent contractions and endothelial dysfunction in human hypertension,” British Journal of Pharmacology, vol. 157, no. 4, pp. 527–536.

11. J. Flammer and T. F. Lüscher (2010). “Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases,” Swiss Medical Weekly, vol. 140, Article ID w13122, 2010.

12. S. Taddei, D. Versari, A. Cipriano et al. (2006). “Identification of a cytochrome P450 2C9-derived endothelium-derived hyperpolarizing factor in essential hypertensive patients,” Journal of the American College of Cardiology, vol. 48, no. 3, pp. 508–515.

13. I. A. M. van den Oever, H. G. Raterman, M. T. Nurmohamed, and S. Simsek (2010). “Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus,” Mediators of In􀄘ammation, vol. 2010, Article ID 792393, 15 pages.

14. Picchi et al. (2006). Tumour Necrosis Factor- α induces Endothelium Dysfunction in the prediabetic metabolic syndrome. American Heart Association.inc.

15. Iwashima, T. et al. (2019). Aronia berry extract inhibits TNF-α-induced vascular endothelial inflammation through regulation of STAT3. Food and nutrition research, page: 1-8.

 16. Gao X, Zhang H, Belmadani S, Wu J, Xu X, Elford H, Potter BJ,Zhang C. (2008). Role of TNF-_-induced reactive oxygen species in endothelial dysfunction during reperfusion injury. Am J Physiol Heart Circ Physiol 295: H2242–H2249.

17. Gao X, et al. (2007). TNF-α contributes to Endothelial Dysfunction by upregulating arginase in Ischemia/ Reperfusion injury. Vascular Biology; 27:1269-1275.