Endothelial expression of the receptor for advanced glycation end products in experimental diabetes

Endothelial expression of the receptor for advanced glycation end products in experimental diabetes

Main Article Content

Nelson Muñoz
Jesús Mosquera
Adriana Pedreáñez

Abstract

The receptor for advanced glycation end products (RAGE) is implicated in the pathogenesis of several chronic diseases including diabetes. The interaction between RAGE and advanced glycation end products (AGEs) promotes gene expression, enhances the release of proinflammatory molecules and causes the generation of oxidative stress in numerous cell types. The aim of this investigation was to evaluate the effect of enalapril and losartan on RAGE expression in abdominal aortic endothelium of rats with experimentally induced diabetes. Male Sprague-Dawley rats, weighing approximately 150 - 200 g, were used. Diabetes was induced in 30 rats by intravenous administration of a single dose of 55 mg/kg body weight of streptozotocin (ETZ). The following groups were studied: control (n=10), diabetic (n=10), losartan-treated diabetic (n=10) and enalapril-treated diabetic (n=10) rats. RAGE expression in aortic endothelium was determined by indirect immunofluorescence. A significant increase in RAGE expression was observed in diabetic animals versus controls (p<0.001), there was a decrease in RAGE expression, in animals treated with losartan versus controls (p<0.01) and in those treated with enalapril (p<0.05) versus control and versus diabetes + vehicle. In conclusion, in the experimental model of ETZ-induced diabetes, there is an increase in RAGE expression at the level of the abdominal aortic endothelium, which can be reversed by treatment with losartan and/or enalapril, two drugs that block the renin-angiotensin system, suggesting its involvement in the molecular events related to vascular damage during diabetes.

References

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