Expresión endotelial del receptor para productos finales de glicación avanzada en diabetes experimental

Expresión endotelial del receptor para productos finales de glicación avanzada en diabetes experimental

Contenido principal del artículo

Nelson Muñoz
Jesús Mosquera
Adriana Pedreáñez

Resumen

El receptor para productos finales de glicación avanzada (RAGE) está implicado en la patogénesis de varias enfermedades crónicas, incluida la diabetes. La interacción entre RAGE y los productos finales de glicación avanzada (AGEs), promueve la expresión génica, potencia la liberación de moléculas proinflamatorias y provoca la generación de estrés oxidativo en numerosos tipos de células. El objetivo de esta investigación fue evaluar el efecto del enalapril y el losartán sobre la expresión de RAGE en el endotelio de la aorta abdominal de ratas con diabetes inducida experimentalmente. Se utilizaron ratas Sprague-Dawley machos, con un peso aproximado de entre 150 - 200 g. La diabetes se indujo en 30 ratas mediante la administración intravenosa de una sola dosis de 55 mg/Kg de peso corporal de estreptozotocina (ETZ). Se estudiaron los siguientes grupos: ratas control (n=10), diabéticas (n=10), diabéticas tratadas con losartán (n=10) y diabéticas tratadas con enalapril (n=10). La expresión de RAGE en el endotelio aórtico se prolonga por inmunofluorescencia indirecta. Se disminuyó un incremento significativo en la expresión de RAGE en los animales diabéticos versus los controles (p<0.001), hubo una disminución en la expresión de RAGE, en los animales tratados con losartán versus los controles (p<0.01) y en los tratados con enalapril (p<0,05) versus control y versus diabetes + vehículo. En conclusión, en el modelo experimental de diabetes inducida por ETZ, existe un incremento en la expresión de RAGE a nivel del endotelio de la aorta abdominal, la cual puede revertirse mediante el tratamiento con losartán y/o enalapril,

Citas

Alegria, JR., Miller, TD., Gibbons, RJ., Yi, QL., Yusuf, S., Collaborative Organization of RheothRx Evaluation (CORE) Trial Investigators (2007). Infarct size, ejection fraction, and mortality in diabetic patients with acute myocardial infarction treated with thrombolytic therapy. American heart journal, 154(4), 743–750. https://doi.org/10.1016/j.ahj.2007.06.020

Anand, DV., Lim, E., Darko, D., Bassett, P., Hopkins, D., Lipkin, D., Corder, R., Lahiri, A. (2007). Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers. Journal of the American College of Cardiology, 50(23), 2218–2225. https://doi.org/10.1016/j.jacc.2007.08.032

Chen, C., Li, L., Qin, H., Huang, Z., Xian, J., Cai, J., Qin, Y., Zhang, J., Liang, X. (2018). Effects of Irbesartan Pretreatment on Pancreatic β-Cell Apoptosis in STZ-Induced Acute Prediabetic Mice. Oxidative medicine and cellular longevity, 2018, 8616194. https://doi.org/10.1155/2018/8616194

Del Turco, S., Basta, G. (2012). An update on advanced glycation endproducts and atherosclerosis. BioFactors (Oxford, England), 38(4), 266–274. https://doi.org/10.1002/biof.1018

El Desoky ES. (2011). Drug therapy of heart failure: an immunologic view. American journal of therapeutics, 18(5), 416–425. https://doi.org/10.1097/MJT.0b013e3181d169db

Goldin, A., Beckman, JA., Schmidt, AM., Creager, M. A. (2006). Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation, 114(6), 597–605. https://doi.org/10.1161/CIRCULATIONAHA.106.621854

Haas, AV., & McDonnell, ME. (2018). Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinology and metabolism clinics of North America, 47(1), 51–63. https://doi.org/10.1016/j.ecl.2017.10.010

Hudson, BI., Lippman, ME. (2018). Targeting RAGE Signaling in Inflammatory Disease. Annual review of medicine, 69, 349–364. https://doi.org/10.1146/annurev-med-041316-085215

Kass DA. (2003). Getting better without AGE: new insights into the diabetic heart. Circulation research, 92(7), 704–706. https://doi.org/10.1161/01.RES.0000069362.52165.C9

Kehm, R., Rückriemen, J., Weber, D., Deubel, S., Grune, T., Höhn, A. (2019). Endogenous advanced glycation end products in pancreatic islets after short-term carbohydrate intervention in obese, diabetes-prone mice. Nutrition & diabetes, 9(1), 9. https://doi.org/10.1038/s41387-019-0077-x

Leung, SS., Forbes, JM., Borg, DJ. (2016). Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis. Current diabetes reports, 16(10), 100. https://doi.org/10.1007/s11892-016-0782-y

Lim, S., Lee, M. E., Jeong, J., Lee, J., Cho, S., Seo, M., Park, S. (2018). sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation. Inflammation research : official journal of the European Histamine Research Society ... [et al.], 67(8), 691–701. https://doi.org/10.1007/s00011-018-1160-9

Miller, AJ., Arnold, AC. (2019). The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 29(2), 231–243. https://doi.org/10.1007/s10286-018-0572-5

Muñoz, M., Rincón, J., Pedreañez, A., Viera, N., Hernández-Fonseca, J. P., Mosquera, J. (2011). Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin. Journal of the renin-angiotensin-aldosterone system : JRAAS, 12(4), 404–412. https://doi.org/10.1177/1470320311410092

Muñoz, N., Pedreañez, A., Mosquera, J. (2020). Angiotensin II Induces Increased Myocardial Expression of Receptor for Advanced Glycation End Products, Monocyte/Macrophage Infiltration and Circulating Endothelin-1 in Rats With Experimental Diabetes. Canadian journal of diabetes, 44(7), 651–656. https://doi.org/10.1016/j.jcjd.2020.03.010

Saku, K., Tahara, N., Takaseya, T., Otsuka, H., Takagi, K., Shojima, T., Shintani, Y., Zaima, Y., Kikusaki, S., Fukuda, T., Oryoji, A., Nishino, Y., Matsui, T., Kakuma, T., Akiba, J., Fukumoto, Y., Yamagishi, SI., Tanaka, H. (2020). Pathological Role of Receptor for Advanced Glycation End Products in Calcified Aortic Valve Stenosis. Journal of the American Heart Association, 9(13), e015261. https://doi.org/10.1161/JAHA.119.015261

Scheen AJ. (2004). Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes & metabolism, 30(6), 487–496. https://doi.org/10.1016/s1262-3636(07)70146-5

Shi, Y., Vanhoutte, PM. (2017). Macro- and microvascular endothelial dysfunction in diabetes. Journal of diabetes, 9(5), 434–449. https://doi.org/10.1111/1753-0407.12521

Smith DH. (2008). Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. Drugs, 68(9), 1207–1225. https://doi.org/10.2165/00003495-200868090-00003

Stefano, GB., Challenger, S., Kream, RM. (2016). Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. European journal of nutrition, 55(8), 2339–2345. https://doi.org/10.1007/s00394-016-1212-2

Teissier, T., Boulanger, É. (2019). The receptor for advanced glycation end-products (RAGE) is an important pattern recognition receptor (PRR) for inflammaging. Biogerontology, 20(3), 279–301. https://doi.org/10.1007/s10522-019-09808-3

Vargas, R., Rincón, J., Pedreañez, A., Viera, N., Hernández-Fonseca, J. P., Peña, C., Mosquera, J. (2012). Role of angiotensin II in the brain inflammatory events during experimental diabetes in rats. Brain research, 1453, 64–76. https://doi.org/10.1016/j.brainres.2012.03.021

Varma, U., Koutsifeli, P., Benson, V. L., Mellor, K. M., Delbridge, L. (2018). Molecular mechanisms of cardiac pathology in diabetes - Experimental insights. Biochimica et biophysica acta. Molecular basis of disease, 1864(5 Pt B), 1949–1959. https://doi.org/10.1016/j.bbadis.2017.10.035

Viigimaa, M., Sachinidis, A., Toumpourleka, M., Koutsampasopoulos, K., Alliksoo, S., Titma, T. (2020). Macrovascular Complications of Type 2 Diabetes Mellitus. Current vascular pharmacology, 18(2), 110–116. https://doi.org/10.2174/1570161117666190405165151

Wang, X., Ye, Y., Gong, H., Wu, J., Yuan, J., Wang, S., Yin, P., Ding, Z., Kang, L., Jiang, Q., Zhang, W., Li, Y., Ge, J., Zou, Y. (2016). The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice. Journal of molecular and cellular cardiology, 97, 180–190. https://doi.org/10.1016/j.yjmcc.2016.05.012

Yamagishi, S., Matsui, T. (2016). Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention. Nutrition (Burbank, Los Angeles County, Calif.), 32(2), 157–165. https://doi.org/10.1016/j.nut.2015.08.001

Yamagishi, SI., Sotokawauchi, A., Matsui, T. (2019). Pathological Role of Advanced Glycation End Products (AGEs) and their Receptor Axis in Atrial Fibrillation. Mini reviews in medicinal chemistry, 19(13), 1040–1048. https://doi.org/10.2174/1389557519666190311140737

Zhou, J., Xu, X., Liu, JJ., Lin, YX., Gao, G. D. (2007). Angiotensin II receptors subtypes mediate diverse gene expression profile in adult hypertrophic cardiomyocytes. Clinical and experimental pharmacology & physiology, 34(11), 1191–1198. https://doi.org/10.1111/j.1440-1681.2007.04694.x