EL ENDOTELIO: ESTRUCTURA, FUNCIÓN Y DISFUNCIÓN ENDOTELIAL
Palabras clave:
Endotelio, disfunción endotelial, aterosclerosis.
Resumen
El endotelio se puede definir como una monocapa que separa los tejidos de la sangre. Las células endoteliales tienen una multitud de funciones que son específicas a su localización. La principal función del endotelio es regular el flujo y la perfusión sistémicos a través de cambios en el diámetro y en el tono vascular. La disfunción endotelial (DE) comprende una pérdida del balance entre los factores vasodilatadores y vasoconstrictores derivados del endotelio, donde el estado vasoconstrictor llega a ser dominante, llevando a cambios patofisiológicos progresivos. Colectivamente, estos cambios endoteliales exhiben características proinflamatorias, prooxidantes, proliferativas, procoagulantes y de adhesión vascular. El proceso de aterosclerosis comienza temprano en la vida y la DE contribuye a la aterogénesis en cada fase de la aterosclerosis. La disfunción endotelial es un marcador de la aterosclerosis y es el precursor más claramente definido de la aterosclerosis. El estrés oxidativo es el mecanismo celular subyacente para el desarrollo de la DE. La inflamación es otro mecanismo subyacente a la DE. Hay una relación causal entre el estrés oxidativo y la inflamación. El estrés oxidativo puede amplificar las vías de señalización vasculares inflamatorias y la inflamación incrementa el estrés oxidativo. La función endotelial puede ser medida mediante su capacidad para ejecutar varias funciones, incluyendo el tono vasomotor, la expresión de moléculas de adhesión y el mantenimiento de un microambiente antitrombótico. En la investigación clínica la función endotelial se detecta midiendo los cambios en el tono vasomotor en respuesta a varios estímulos. Un número de biomarcadores se han identificado y utilizado como indicadores de función endotelial.
Citas
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.
Publicado
2020-11-13
Cómo citar
Carvajal Carvajal, C. (2020). EL ENDOTELIO: ESTRUCTURA, FUNCIÓN Y DISFUNCIÓN ENDOTELIAL. Medicina Legal De Costa Rica, 34(2). Recuperado a partir de //www.binasss.sa.cr/ojssalud/index.php/mlcr/article/view/74
Sección
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La propiedad intelectual de los trabajos aceptados es de sus autores, no obstante el acceso a ellos es totalmente abierto y gratuito, por lo que podrán ser reproducidos total o parcialmente con la única limitación de reconocer la autoría y la fuente de publicación ( Revista Medicina Legal de Costa Rica), siempre y cuando dicha explotación no tenga carácter comercial.
