Papel de la disfunción endotelial en pacientes con hepatopatía crónica e hipertensión portal
DOI:
https://doi.org/10.59093/27112330.174Palabras clave:
endotelio, enfermedad hepática, hipertensión portal, síndrome metabólico.Resumen
La disfunción endotelial desempeña un papel central en la fisiopatología de la hepatopatía crónica y la hipertensión portal, contribuyendo al aumento de la resistencia vascular intrahepática y a la progresión de la enfermedad. En el contexto de la enfermedad hepática esteatósica asociada a disfunción metabólica, la disfunción endotelial se asocia con resistencia a la insulina, inflamación crónica y progresión de la fibrosis hepática, actuando como un vínculo entre la enfermedad hepática y el daño sistémico. El objetivo de esta revisión es integrar los mecanismos fisiopatológicos de la disfunción endotelial en la hipertensión portal, junto con el componente metabólico emergente de la enfermedad hepática esteatósica asociada a disfunción metabólica, proponiendo una visión unificada de la enfermedad hepática como un proceso sistémico. Asimismo, se discuten las principales implicaciones clínicas y las estrategias terapéuticas actuales. La evidencia actual posiciona a la disfunción endotelial como un mecanismo central en la hipertensión portal, al integrar alteraciones vasculares, metabólicas e inflamatorias en un mismo eje patogénico. Además, se vincula con la resistencia a la insulina, la inflamación crónica y la progresión del daño hepático. Los tratamientos actuales se enfocan principalmente en la reducción de la presión portal y el manejo de las complicaciones, por lo que se evidencia la necesidad de desarrollar estrategias dirigidas a modular la función endotelial y, a su vez, establecer su papel en la práctica clínica.
Descargas
Referencias bibliográficas
Miao L, Targher G, Byrne CD, Cao YY, Zheng MH. Current status and future trends of the global burden of MASLD. Trends Endocrinol Metab 2024;35:697–707. https://doi.org/10.1016/j.tem.2024.02.007.
Eslam M, Newsome PN, Sarin SK, Anstee QM, Targher G, Romero-Gomez M, et al. A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement. J Hepatol 2020;73:202–209. https://doi.org/10.1016/j.jhep.2020.03.039.
Sharma S, Le Guillou D, Chen JY. Cellular stress in the pathogenesis of nonalcoholic steatohepatitis and liver fibrosis. Nat Rev Gastroenterol Hepatol 2023;20:662–678. https://doi.org/10.1038/s41575-023-00832-w.
Gracia-Sancho J, Marrone G, Fernández-Iglesias A. Hepatic microcirculation and mechanisms of portal hypertension. Nat Rev Gastroenterol Hepatol 2019;16:221–234. https://doi.org/10.1038/s41575-018-0097-3.
Ruiz-Manriquez J, Olivas-Martinez A, Chávez-García LC, Fernández-Ramírez A, Moctezuma-Velazquez C, Kauffman-Ortega E, et al. Prevalence of Metabolic-associated Fatty Liver Disease in Mexico and Development of a Screening Tool: The MAFLD-S Score. Gastro Hep Adv 2022;1:352–358. https://doi.org/10.1016/j.gastha.2021.12.011.
Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet 2021;398:1359–1376. https://doi.org/10.1016/S0140-6736(21)01374-X.
Felli E, Nulan Y, Ortega-Ribera M, Fernández-Iglesias A, Gracia-Sancho J. The role of liver sinusoidal endothelial cells in liver diseases: Key players in health and pathology. J Hepatol 2026;84:655–672. https://doi.org/10.1016/j.jhep.2025.10.017.
Iwakiri Y. Endothelial dysfunction in the regulation of cirrhosis and portal hypertension. Liver Int 2012;32:199–213. https://doi.org/10.1111/j.1478-3231.2011.02579.x.
Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The Vascular Endothelium and Human Diseases. Int J Biol Sci 2013;9:1057–1069. https://doi.org/10.7150/ijbs.7502.
Barac A, Campia U, Panza JA. Methods for Evaluating Endothelial Function in Humans. Hypertension 2007;49:748–760. https://doi.org/10.1161/01.HYP.0000259601.38807.a6.
London NR, Whitehead KJ, Li DY. Endogenous endothelial cell signaling systems maintain vascular stability. Angiogenesis 2009;12:149–158. https://doi.org/10.1007/s10456-009-9130-z.
Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol 2006;291:H985–H1002. https://doi.org/10.1152/ajpheart.00292.2006.
Gaengel K, Genové G, Armulik A, Betsholtz C. Endothelial-Mural Cell Signaling in Vascular Development and Angiogenesis. Arterioscler Thromb Vasc Biol 2009;29:630–638. https://doi.org/10.1161/ATVBAHA.107.161521.
Aird WC. Coagulation. Crit Care Med 2005;33:S485–S487. https://doi.org/10.1097/01.CCM.0000186267.66402.24.
Verhamme P, Hoylaerts MF. The pivotal role of the endothelium in haemostasis and thrombosis. Acta Clin Belg 2006;61:213–219. https://doi.org/10.1179/acb.2006.036.
Wilcox JN, Subramanian RR, Sundell CL, Tracey WR, Pollock JS, Harrison DG, et al. Expression of Multiple Isoforms of Nitric Oxide Synthase in Normal and Atherosclerotic Vessels. Arterioscler Thromb Vasc Biol 1997;17:2479–2488. https://doi.org/10.1161/01.ATV.17.11.2479.
Drexler H. Factors involved in the maintenance of endothelial function. Am J Cardiol 1998;82:3S–4S. https://doi.org/10.1016/S0002-9149(98)00667-5.
Taylor SA, Bader GD, MacParland S, Mullen AC, Andrews T, Cuenca AG, et al. Towards a reference cell atlas of liver diversity over the human lifespan. Nat Rev Gastroenterol Hepatol 2026;23:97–109. https://doi.org/10.1038/s41575-025-01114-3.
DeLeve LD. Liver sinusoidal endothelial cells in hepatic fibrosis. Hepatology 2015;61:1740–1746. https://doi.org/10.1002/hep.27376.
Lerman A, Zeiher AM. Endothelial Function. Circulation 2005;111:363–368. https://doi.org/10.1161/01.CIR.0000153339.27064.14.
Siti HN, Kamisah Y, Kamsiah J. The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review). Vascul Pharmacol 2015;71:40–56. https://doi.org/10.1016/j.vph.2015.03.005.
Allameh A, Niayesh-Mehr R, Aliarab A, Sebastiani G, Pantopoulos K. Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants (Basel) 2023;12:1653. https://doi.org/10.3390/antiox12091653.
Ibarrola-Calleja JL, Núñez BF, Rodríguez GM, Ordóñez-Céspedes J. Hipertensión portal. Acta Med Grupo Angeles 2023;21:s57–s65. https://doi.org/10.35366/109564.
Narváez-Rivera RM, Cortez-Hernández CA, González-González JA, Tamayo-de la Cuesta JL, Zamarripa-Dorsey F, Torre-Delgadillo A, et al. Consenso Mexicano de Hipertensión Portal. Rev Gastroenterol Mex 2013;78:92–113. https://doi.org/10.1016/j.rgmx.2013.01.006.
Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: Too much, not enough. Hepatology 2002;35:478–491. https://doi.org/10.1053/jhep.2002.31432.
Bosch J. Vascular Deterioration in Cirrhosis. J Clin Gastroenterol 2007;41:S247–S253. https://doi.org/10.1097/MCG.0b013e3181572357.
Escorsell A, Bosch J. Pathophysiology of variceal bleeding. In: Portal Hypertension in the 21st Century. Dordrecht: Springer Netherlands; 2004:155–166. https://doi.org/10.1007/978-94-007-1042-9_18.
Fernandez M, Vizzutti F, Garcia-Pagan JC, Rodes J, Bosch J. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology 2004;126:886–894. https://doi.org/10.1053/j.gastro.2003.12.012.
Alqahtani SA, Jang S. Pathophysiology and Management of Variceal Bleeding. Drugs 2021;81:647–667. https://doi.org/10.1007/s40265-021-01493-2.
Kim YS. Ascites, Hepatorenal Syndrome and Spontaneous Bacterial Peritonitis in Patients with Portal Hypertension. Korean J Gastroenterol 2010;56:168–175. https://doi.org/10.4166/kjg.2010.56.3.168.
Huh Y, Cho YJ, Nam GE. Recent Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease. J Obes Metab Syndr 2022;31:17–27. https://doi.org/10.7570/jomes22021.
Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, et al. EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024;81:492–542. https://doi.org/10.1016/j.jhep.2024.04.031.
Paul S, Ali A, Katare R. Molecular complexities underlying the vascular complications of diabetes mellitus – A comprehensive review. J Diabetes Complications 2020;34:107613. https://doi.org/10.1016/j.jdiacomp.2020.107613.
Potenza MA, Addabbo F, Montagnani M. Vascular actions of insulin with implications for endothelial dysfunction. Am J Physiol Endocrinol Metab 2009;297:E568–E577. https://doi.org/10.1152/ajpendo.00297.2009.
Ogresta D, Mrzljak A, Cigrovski Berkovic M, Bilic-Curcic I, Stojsavljevic-Shapeski S, Virovic-Jukic L. Coagulation and Endothelial Dysfunction Associated with NAFLD: Current Status and Therapeutic Implications. J Clin Transl Hepatol 2022;10:339–355. https://doi.org/10.14218/JCTH.2021.00268.
Fujimoto M, Shimizu N, Kunii K, Martyn JAJ, Ueki K, Kaneki M. A Role for iNOS in Fasting Hyperglycemia and Impaired Insulin Signaling in the Liver of Obese Diabetic Mice. Diabetes 2005;54:1340–1348. https://doi.org/10.2337/diabetes.54.5.1340.
Cybulsky MI, Gimbrone MA. Endothelial Expression of a Mononuclear Leukocyte Adhesion Molecule During Atherogenesis. Science 1991;251:788–791. https://doi.org/10.1126/science.1990440.
Smalley DM, Lin JHC, Curtis ML, Kobari Y, Stemerman MB, Pritchard KA. Native LDL Increases Endothelial Cell Adhesiveness by Inducing Intercellular Adhesion Molecule–1. Arterioscler Thromb Vasc Biol 1996;16:585–590. https://doi.org/10.1161/01.ATV.16.4.585.
Kumar S, Duan Q, Wu R, Harris EN, Su Q. Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis. Adv Drug Deliv Rev 2021;176:113869. https://doi.org/10.1016/j.addr.2021.113869.
Simonetto DA, Gines P, Kamath PS. Hepatorenal syndrome: pathophysiology, diagnosis, and management. BMJ 2020;m2687. https://doi.org/10.1136/bmj.m2687.
Mantovani A, Csermely A, Petracca G, Beatrice G, Corey KE, Simon TG, et al. Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2021;6:903–913. https://doi.org/10.1016/S2468-1253(21)00308-3.
Lonardo A, Mantovani A, Targher G, Baffy G. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications. Int J Mol Sci 2022;23:13320. https://doi.org/10.3390/ijms232113320.
Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond) 2011;120:357–375. https://doi.org/10.1042/CS20100476.
Loke KE, Curran CML, Messina EJ, Laycock SK, Shesely EG, Carretero OA, et al. Role of Nitric Oxide in the Control of Cardiac Oxygen Consumption in B₂-Kinin Receptor Knockout Mice. Hypertension 1999;34:563–567. https://doi.org/10.1161/01.HYP.34.4.563.
Abraldes JG, Albillos A, Bañares R, Turnes J, González R, García-Pagán JC, et al. Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: A Randomized Controlled Trial. Gastroenterology 2009;136:1651–1658. https://doi.org/10.1053/j.gastro.2009.01.043.
Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res 2017;120:229–243. https://doi.org/10.1161/CIRCRESAHA.116.308537.
Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med 2021;384:1113–1124. https://doi.org/10.1056/NEJMoa2028395.
Bosch J, Abraldes J, Berzigotti A, Garcia-Pagan J. Portal Hypertension and Gastrointestinal Bleeding. Semin Liver Dis 2008;28:3–25. https://doi.org/10.1055/s-2008-1040318.
Villanueva C, Albillos A, Genescà J, Garcia-Pagan JC, Calleja JL, Aracil C, et al. β blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2019;393:1597–1608. https://doi.org/10.1016/S0140-6736(18)31875-0.
Bath PM, Krishnan K, Appleton JP. Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke. Cochrane Database Syst Rev 2017;2017:CD000398. https://doi.org/10.1002/14651858.CD000398.pub2.
Yang Y, Yu T, Lian YJi, Ma R, Yang S, Cho JY. Nitric oxide synthase inhibitors: a review of patents from 2011 to the present. Expert Opin Ther Pat 2015;25:49–68. https://doi.org/10.1517/13543776.2014.979154.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2026 Los autores conservan todos los derechos de autor y otorgan a la Asociación Colombiana de Hepatología un derecho no exclusivo para publicar y difundir su trabajo.
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
La política de reconocimiento de autoría de Hepatología se basa en los criterios indicados por el ICMJE para conferir crédito de un trabajo a una persona, a la vez que se le atribuye responsabilidad por la publicación del mismo.
| Estadísticas de artículo | |
|---|---|
| Vistas de resúmenes | |
| Vistas de PDF | |
| Descargas de PDF | |
| Vistas de HTML | |
| Otras vistas | |
