THE ENDOTHELIUM: ENDOTHELIAL STRUCTURE, FUNCTION AND DYSFUNCTION
Keywords:
Endothelium, endothelial dysfunction, atherosclerosis.Abstract
The endothelium could be defined as a cellular monolayer separating all tissues from the bloodflow. Endothelial cells have a myriad of functions that are specific to their location. The main function of endothelium is to regulate systemic blood flow and tissue perfusión through changes in vessel diameter and tone vascular. Endothelial dysfunction (ED) comprises a loss of balance between endothelial-derived vasodilatory and vasoconstrictory factors, where the pro-vasoconstrictory state become dominant, leading to progressive pathophysiological changes. Collectively, these endothelial changes exhibit proinflammatory, pro-oxidant, proliferative, procoagulation and pro-vascular adhesion features. The process of atherosclerosis begins early in life, and endothelial dysfunction contributes to atherogenesis at every phase of atherosclerosis. Endothelial dysfunction is a marker of atherosclerosis and it is the most clearly defined early precursor of atherosclerosis. Oxidative stress to be the common underlying cellular mechanisms for the development of ED. Inflammation is another common underlying mechanism of ED. There is a causal relationship between oxidative stress and inflammation. Oxidative stress may amplify vascular inflammation signalling pathways, and conversely inflammation increases oxidative stress. Endothelial function can be assessed by assaying its capacity to perform its various functions, including regulation of vasomotor tone, expression of adhesion molecules and maintenance of an anti-thrombotic microenvironment. In clinical Research, endothelial function is tipically assessed by measuring changes in vasomotor tone in response to various stimuli. A number of biomarkers have been identified and used as indicators of endothelial function.
References
1. Widlansky, M. & Gutlerman, D. (2011). Regulation of endothelial function by mitochondrial reactive oxigen species. Antioxidants & Redox Signaling, 15(6), 1517-1530.
2. Mudau, M., Genis, A., Lochner, A. & Strijdom, H. (2012). Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr, 23(4), 222-231.
3. Steyers, C. & Miller, F. (2014). Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci, 15, 11324- 11349.
4. Seals, D., Jablonski, K. & Donato, A. (2012). Aging and vascular endothelial functions in humans. Clin Sci, 120(9), 357-375.
5. Castellon, X. & Bogdanova, V. (2016). Chronic inflammatory diseases and endothelial dysfunction. Aging and Disease, 7(1), 81-89.
6. Augustin, H., Kozian, D. & Johnson, R. C. (1994). Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. BioEssays, 16(12), 901–906.
7. Favero, G., Paganelli, C., Buffoli, B., Rodella, L. & Rezzani R. (2014). Endothelium and its alterations in cardiovascular diseases: life style intervention. BioMed Research Int, 2014, 1-28.
8. Aird, W. (2012). Endothelial cell heterogeneity. Cold Spring Harb Perspect Med, 2, 1-13.
9. Rodrígues, S. & Granger, D. (2015). Blood cells and endothelial barrier function. Tissue barriers, 3(1-2), e978720-1- -e978720-11.
10. Chistiakov, D., Orekhov, A. & Bobryshev Y. (2015). Endothelial barrier and its abnormalities in cardiovascular disease. Frontiers in Physiology, 6, 1-11.
11. Culic, O., Gruwel, M. L. & Schrader, J. (1997). Energy turnover of vascular endothelial cells. Am J Physiol, 273, C205 – C213.
12. Goveia, J., Stapor, P. & Carmeliet, P. (2014). Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease. EMBO Mol Med, 6, 1105-1120.
13. Su, J. B. (2015). Vascular endothelial dysfunction and pharmacological treatment. World J Cardiology, 7(11), 719-741.
14. Park, K. H. & Park, W.J. (2015). Endothelial dysfunction: clinical implications in cardiovascular disease and therapeutic approaches. Rev Cardiovascular Disorders, 30, 1213-1225.
15. Rajendran, P., Rengarajan, T., Thangavel, J., Nishigaki, Y., Sakthisekaran, D., Sethi, G. & Nishigaki, I. (2013). The vascular endothelium and human diseases. Int J Biol Sci, 9, 1057-1069.
16. Yau, J., Teoh, H. & Verma, S. (2015). Endothelial cell control of thrombosis. BMC Cardiovasc Disorders, 15,1-11.
17. Mikhed, Y., Daiber, A. & Steven, S. (2015). Mitochondrial oxidative stress, mitochondrial DNA damage and their role in age-related vascular dysfunction. Int J Mol Sci, 16, 15918-15953.
18. Hamilton, S. & Watts, G. (2013). Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Review of Diabetic Studies, 10, 133-156.
19. Förstermann, U. & Sessa, W. (2012). Nitric oxide synthases: regulation and function. European Heart J, 33, 829-837.
20. Shimokawa, H. & Godo, S. (2016). Diverse functions of endothelial NO synthase system: O and EDH. J Cardiovasc Pharmacol, 67(5), 361-366.
21. Strijdom, H., Chamane, N. & Lochner, A. (2009). Nitric oxide in the cardiovascular system: a simple molecule with complex actions. Cardiovasc J Afr, 20, 303–310.
22. Muniyappa, R. & Sowers, J. (2013). Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord, 14, 1, 5-12.
23. Matsuzawa, Y. & Lerman, A. (2014). Endothelial dysfunction and coronary artery disease: assessment, prognosis and treatment. Coron Artery Dis, 25(8), 713-724.
24. Hadi, H., Carr, C. & Suwaidi, J. (2005). Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vascular Health and Risk Management, 1(3), 183-198.
25. Heiss, C., Rodríguez-Mateos, A. & Kelm, M. (2015). Central role of eNOS in the maintenance of endothelial homeostasis. Antioxidants & Redox Signaling, 22(14), 1230-1242.
26. Rigor, R., Shen, Q., Pivetti, C., Wu, M. & Yuan, S. (2013). Myosin light chain kinase signaling in endothelial barrier dysfunction. Med Res Rev, 33(5), 911-933.
27. Kolka, C. & Bergman, R. (2012). The barrier within: endothelial transport of hormones. Physiology (Bethesda), 27, 4, 237-247.
28. Fels, J., Jeggle, P., Liashkovich, I., Peters, W. & Oberleithner, H. (2014). Nanomechanics of vascular endothelium. Cell Tissue Res, 355, 727-737.
29. Flammer, A., Anderson, T., Celermajer, D., Creager, M., Deanfield, J., Ganz, P., et al. (2012). The assessment of endothelial function-from Research into clinical practice. Circulation, 126(6), 753-767.
30. Thosar, S., Johnson, B., Johnston, J. & Wallace, J. (2012). Sitting and endothelial dysfunction: the role of shear stress. Med Sci Monit, 18(12), RA173-180.
31. Symons, J. D. & Abel, E. D. (2013). Lipotoxicity contributes to endothelial dysfunction: a focus on the contribution from ceramide. Rev Endocr Metab Disord, 14(1), 59-68.
32. Gimbrone, M., & García-Cardeña, G. (2013). Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc Pathol, 22(1), 9-15.
33. Collins, C. & Tzima, E. (2011). Hemodynamic forces in endothelial dysfunction and vascular aging. Exp Gerontol, 46(2-3), 185-188.
34. Lenna, S., Han, R. & Trojanowska, M. (2014). ER stress and endothelial dysfunction. IUBMB Life, 66(8), 530-537.
35. Tang, X., Luo, Y. X., Chen, H. Z. & Liu, D. P. (2014). Mitochondria, endothelial cell function, and vascular diseases. Frontiers in Physiology, 5, 1-17.
36. Tabas, I., García-Cardeña, G. & Owens, G. K. (2015). Recent insights into the cellular biology of atherosclerosis. Cell Biology, 209(1), 13-22.
37. Zhou, J., Li, Y. S. & Chien, S. (2014). Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol, 34(10), 2191-2198.
38. Liao, J. (2013). Linking endothelial dysfunction with endothelial cell activation. J Clin Investigation, 123, 540-541.
39. Funk, S., Yurdagul Jr, A. & Orr, W. (2012). Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med, 2012,1-19.
40. Rabelo, L., Ferreira, F., Nunes-Souza, V., da Fonseca, L. & Goulart, M. (2015). Arginase as a critical prooxidant mediator in the binomial endothelial dysfunction-atherosclerosis. Oxidative Medicine and Cellular Longevity, 2015, 1-12.
41. Paneni, F., Beckman, J. & Creager, M. (2013). Diabetes and vascular disease: pathophysiology, clinical Consequences, and medical therapy: part I. European Heart J, 34, 2436-2446.
42. Galogahi, K. K., Liu, C. C., Gentile, C., kok, C., Nunez, A. & Garcia, A. (2014). Glutathionylation mediates angiotensin II–Induced eNOS uncoupling, amplifying NADPH Oxidase-dependent endothelial dysfunction. J Americ Heart Assoc, 3, 1-11.
43. Hwang, M. H. & Kim, S. (2014). Type 2 diabetes: endothelial dysfunction and exercise. J Exerc Nutr Biochem, 18(3), 239-247.
44. Huang, A., Yang, Y. M., Feher, A., Bagi, Z., Kaley, G. & Sun, D. (2012). Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. Am J Physiol Regul Integr Comp Physiol, 302, R674-R681.
45. Heo, K. S., Fujiwara, K. & Abe, J. I. (2011). Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ J, 75(12), 2722-2730.
46. Dinh, Q., Drummond, G., Sobey, C. & Chrissobolis, S. (2014). Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. BioMed Research Int, 2014, 1-11.
47. Davies, P., Civelek, M., Fang, Y. & Fleming, I. (2013). The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovascular Research, 99, 315-327.
48. Yin, K. & Agrawal, D. (2014). High density lipoprotein: a novel target for anti-restenosis therapy. Clin Transl Sci, 7(6), 500-511.
49. Rye, K. A. & Barter, P. (2014). Cardioprotective functions of HDLs. J Lipid Research, 55, 168-178.
50. Tran-Dinh, A., Diallo, D., Varela-Pérez, L., Dang, Q.B., Lapergue, B., Burillo, E., et al. (2013). HDL and endotelial Protection. British J Pharmacology, 169, 493-511.
51. Gutiérrez, E., Flammer, A., Lerman, L., Elizaga, J., Lerman, A. & Fernández-Avilés, F. (2013). Endothelial dysfunction over the course of coronary artery disease. European Heart Journal, 34, 3175-3181.
52. Vairappan, B. (2015). Endothelial dysfunction in cirrosis: role of inflammation and oxidative stress. World J Hepatology, 7(3), 443-459.
53. Helbing, T., Olivier, C., Bode, C., Moser, M. & Diehl, P. (2014). Role of microparticles in endothelial dysfunction and arterial hypertension. World J Cardiol, 6(11), 1135-1139.
54. Paudel, K., Panth, N. & Kim, DW. (2016). Circulating endothelial microparticles: a key hallmark of atherosclerosis progression. Scientifica, 2016, 1-9.
55. Nunes-Franca, C., de Oliveira-Izar, M. C., do Amaral, J., Melo-Tegani, D. & Helfenstein-Fonseca, A. (2010). Microparticles as potential biomarkers of cardiovascular disease. Arq Bras Cardiol, 104(2), 169-174.
56. Thomashow, M., Shimbo, D., Parikh, M., Hoffman, E., Vogel-Claussen, J., Hueper, K., et al. (2013). Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. Am J Respir Crit Care Med, 188(1), 60-68.
2. Mudau, M., Genis, A., Lochner, A. & Strijdom, H. (2012). Endothelial dysfunction: the early predictor of atherosclerosis. Cardiovasc J Afr, 23(4), 222-231.
3. Steyers, C. & Miller, F. (2014). Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci, 15, 11324- 11349.
4. Seals, D., Jablonski, K. & Donato, A. (2012). Aging and vascular endothelial functions in humans. Clin Sci, 120(9), 357-375.
5. Castellon, X. & Bogdanova, V. (2016). Chronic inflammatory diseases and endothelial dysfunction. Aging and Disease, 7(1), 81-89.
6. Augustin, H., Kozian, D. & Johnson, R. C. (1994). Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. BioEssays, 16(12), 901–906.
7. Favero, G., Paganelli, C., Buffoli, B., Rodella, L. & Rezzani R. (2014). Endothelium and its alterations in cardiovascular diseases: life style intervention. BioMed Research Int, 2014, 1-28.
8. Aird, W. (2012). Endothelial cell heterogeneity. Cold Spring Harb Perspect Med, 2, 1-13.
9. Rodrígues, S. & Granger, D. (2015). Blood cells and endothelial barrier function. Tissue barriers, 3(1-2), e978720-1- -e978720-11.
10. Chistiakov, D., Orekhov, A. & Bobryshev Y. (2015). Endothelial barrier and its abnormalities in cardiovascular disease. Frontiers in Physiology, 6, 1-11.
11. Culic, O., Gruwel, M. L. & Schrader, J. (1997). Energy turnover of vascular endothelial cells. Am J Physiol, 273, C205 – C213.
12. Goveia, J., Stapor, P. & Carmeliet, P. (2014). Principles of targeting endothelial cell metabolism to treat angiogenesis and endothelial cell dysfunction in disease. EMBO Mol Med, 6, 1105-1120.
13. Su, J. B. (2015). Vascular endothelial dysfunction and pharmacological treatment. World J Cardiology, 7(11), 719-741.
14. Park, K. H. & Park, W.J. (2015). Endothelial dysfunction: clinical implications in cardiovascular disease and therapeutic approaches. Rev Cardiovascular Disorders, 30, 1213-1225.
15. Rajendran, P., Rengarajan, T., Thangavel, J., Nishigaki, Y., Sakthisekaran, D., Sethi, G. & Nishigaki, I. (2013). The vascular endothelium and human diseases. Int J Biol Sci, 9, 1057-1069.
16. Yau, J., Teoh, H. & Verma, S. (2015). Endothelial cell control of thrombosis. BMC Cardiovasc Disorders, 15,1-11.
17. Mikhed, Y., Daiber, A. & Steven, S. (2015). Mitochondrial oxidative stress, mitochondrial DNA damage and their role in age-related vascular dysfunction. Int J Mol Sci, 16, 15918-15953.
18. Hamilton, S. & Watts, G. (2013). Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Review of Diabetic Studies, 10, 133-156.
19. Förstermann, U. & Sessa, W. (2012). Nitric oxide synthases: regulation and function. European Heart J, 33, 829-837.
20. Shimokawa, H. & Godo, S. (2016). Diverse functions of endothelial NO synthase system: O and EDH. J Cardiovasc Pharmacol, 67(5), 361-366.
21. Strijdom, H., Chamane, N. & Lochner, A. (2009). Nitric oxide in the cardiovascular system: a simple molecule with complex actions. Cardiovasc J Afr, 20, 303–310.
22. Muniyappa, R. & Sowers, J. (2013). Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord, 14, 1, 5-12.
23. Matsuzawa, Y. & Lerman, A. (2014). Endothelial dysfunction and coronary artery disease: assessment, prognosis and treatment. Coron Artery Dis, 25(8), 713-724.
24. Hadi, H., Carr, C. & Suwaidi, J. (2005). Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vascular Health and Risk Management, 1(3), 183-198.
25. Heiss, C., Rodríguez-Mateos, A. & Kelm, M. (2015). Central role of eNOS in the maintenance of endothelial homeostasis. Antioxidants & Redox Signaling, 22(14), 1230-1242.
26. Rigor, R., Shen, Q., Pivetti, C., Wu, M. & Yuan, S. (2013). Myosin light chain kinase signaling in endothelial barrier dysfunction. Med Res Rev, 33(5), 911-933.
27. Kolka, C. & Bergman, R. (2012). The barrier within: endothelial transport of hormones. Physiology (Bethesda), 27, 4, 237-247.
28. Fels, J., Jeggle, P., Liashkovich, I., Peters, W. & Oberleithner, H. (2014). Nanomechanics of vascular endothelium. Cell Tissue Res, 355, 727-737.
29. Flammer, A., Anderson, T., Celermajer, D., Creager, M., Deanfield, J., Ganz, P., et al. (2012). The assessment of endothelial function-from Research into clinical practice. Circulation, 126(6), 753-767.
30. Thosar, S., Johnson, B., Johnston, J. & Wallace, J. (2012). Sitting and endothelial dysfunction: the role of shear stress. Med Sci Monit, 18(12), RA173-180.
31. Symons, J. D. & Abel, E. D. (2013). Lipotoxicity contributes to endothelial dysfunction: a focus on the contribution from ceramide. Rev Endocr Metab Disord, 14(1), 59-68.
32. Gimbrone, M., & García-Cardeña, G. (2013). Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis. Cardiovasc Pathol, 22(1), 9-15.
33. Collins, C. & Tzima, E. (2011). Hemodynamic forces in endothelial dysfunction and vascular aging. Exp Gerontol, 46(2-3), 185-188.
34. Lenna, S., Han, R. & Trojanowska, M. (2014). ER stress and endothelial dysfunction. IUBMB Life, 66(8), 530-537.
35. Tang, X., Luo, Y. X., Chen, H. Z. & Liu, D. P. (2014). Mitochondria, endothelial cell function, and vascular diseases. Frontiers in Physiology, 5, 1-17.
36. Tabas, I., García-Cardeña, G. & Owens, G. K. (2015). Recent insights into the cellular biology of atherosclerosis. Cell Biology, 209(1), 13-22.
37. Zhou, J., Li, Y. S. & Chien, S. (2014). Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol, 34(10), 2191-2198.
38. Liao, J. (2013). Linking endothelial dysfunction with endothelial cell activation. J Clin Investigation, 123, 540-541.
39. Funk, S., Yurdagul Jr, A. & Orr, W. (2012). Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes. Int J Vasc Med, 2012,1-19.
40. Rabelo, L., Ferreira, F., Nunes-Souza, V., da Fonseca, L. & Goulart, M. (2015). Arginase as a critical prooxidant mediator in the binomial endothelial dysfunction-atherosclerosis. Oxidative Medicine and Cellular Longevity, 2015, 1-12.
41. Paneni, F., Beckman, J. & Creager, M. (2013). Diabetes and vascular disease: pathophysiology, clinical Consequences, and medical therapy: part I. European Heart J, 34, 2436-2446.
42. Galogahi, K. K., Liu, C. C., Gentile, C., kok, C., Nunez, A. & Garcia, A. (2014). Glutathionylation mediates angiotensin II–Induced eNOS uncoupling, amplifying NADPH Oxidase-dependent endothelial dysfunction. J Americ Heart Assoc, 3, 1-11.
43. Hwang, M. H. & Kim, S. (2014). Type 2 diabetes: endothelial dysfunction and exercise. J Exerc Nutr Biochem, 18(3), 239-247.
44. Huang, A., Yang, Y. M., Feher, A., Bagi, Z., Kaley, G. & Sun, D. (2012). Exacerbation of endothelial dysfunction during the progression of diabetes: role of oxidative stress. Am J Physiol Regul Integr Comp Physiol, 302, R674-R681.
45. Heo, K. S., Fujiwara, K. & Abe, J. I. (2011). Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction. Circ J, 75(12), 2722-2730.
46. Dinh, Q., Drummond, G., Sobey, C. & Chrissobolis, S. (2014). Roles of inflammation, oxidative stress, and vascular dysfunction in hypertension. BioMed Research Int, 2014, 1-11.
47. Davies, P., Civelek, M., Fang, Y. & Fleming, I. (2013). The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovascular Research, 99, 315-327.
48. Yin, K. & Agrawal, D. (2014). High density lipoprotein: a novel target for anti-restenosis therapy. Clin Transl Sci, 7(6), 500-511.
49. Rye, K. A. & Barter, P. (2014). Cardioprotective functions of HDLs. J Lipid Research, 55, 168-178.
50. Tran-Dinh, A., Diallo, D., Varela-Pérez, L., Dang, Q.B., Lapergue, B., Burillo, E., et al. (2013). HDL and endotelial Protection. British J Pharmacology, 169, 493-511.
51. Gutiérrez, E., Flammer, A., Lerman, L., Elizaga, J., Lerman, A. & Fernández-Avilés, F. (2013). Endothelial dysfunction over the course of coronary artery disease. European Heart Journal, 34, 3175-3181.
52. Vairappan, B. (2015). Endothelial dysfunction in cirrosis: role of inflammation and oxidative stress. World J Hepatology, 7(3), 443-459.
53. Helbing, T., Olivier, C., Bode, C., Moser, M. & Diehl, P. (2014). Role of microparticles in endothelial dysfunction and arterial hypertension. World J Cardiol, 6(11), 1135-1139.
54. Paudel, K., Panth, N. & Kim, DW. (2016). Circulating endothelial microparticles: a key hallmark of atherosclerosis progression. Scientifica, 2016, 1-9.
55. Nunes-Franca, C., de Oliveira-Izar, M. C., do Amaral, J., Melo-Tegani, D. & Helfenstein-Fonseca, A. (2010). Microparticles as potential biomarkers of cardiovascular disease. Arq Bras Cardiol, 104(2), 169-174.
56. Thomashow, M., Shimbo, D., Parikh, M., Hoffman, E., Vogel-Claussen, J., Hueper, K., et al. (2013). Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. Am J Respir Crit Care Med, 188(1), 60-68.
Downloads
Published
2020-11-13
Issue
Section
Literature review
License
The intellectual property of accepted works belongs to their authors, however access to them is totally open and free, so they can be reproduced totally or partially with the only limitation of recognizing the authorship and the source of publication (Revista Medicina Legal de Costa Rica), as long as said exploitation does not have commercial character.
How to Cite
THE ENDOTHELIUM: ENDOTHELIAL STRUCTURE, FUNCTION AND DYSFUNCTION. (2020). Medicina Legal De Costa Rica, 34(2). https://www.binasss.sa.cr/ojssalud/index.php/mlcr/article/view/74
