Losartan Decreases Receptor Expression for Advanced Glycation Compounds in Heart Tissue of Diabetic Rats
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Published:
Apr 23, 2021
Keywords:
diabetes, enalapril, losartan, myocardial, RAGE
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Abstract
The receptor for advanced glycation end products (RAGE) can interact with various ligands and induce inflammatory processes. The aim of this research was to determine the effect of enalapril and losartan on the expression of RAGE in cardiac tissue in an experimental model of diabetes. Male Sprague-Dawley rats weighing 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 (STZ). The following groups were studied: control, diabetic, losartan-treated and enalapril-treated diabetic rats. The RAGE expression in myocardium was determined by indirect immunofluorescence. A significant increase in the RAGE expression was observed in diabetic animals versus controls (p<0.01), there was a decrease in myocardial RAGE expression, only in animals treated with losartan versus untreated diabetics (p<0.05). In conclusion, in the experimental model of STZ-induced diabetes, there is an increase in myocardial RAGE expression, which can be reversed by treatment with losartan indicating the involvement of the angiotensin renin system in the mechanisms related to heart damage during diabetes.
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Muñoz N, Mosquera J, Pedreañez Santana A. Losartan Decreases Receptor Expression for Advanced Glycation Compounds in Heart Tissue of Diabetic Rats. REMCB [Internet]. 2021Apr.23 [cited 2024Jul.3];42(1). Available from: https://remcb-puce.edu.ec/remcb/article/view/883
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References
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Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. 2014. Therapeutic approaches to diabetic nephropathy--beyond the RAS. Nat Rev Nephro. 10(6): 325–346.
Goldin A, Beckman JA, Schmidt AM, Creager MA. 2006. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 114(6): 597–605.
Haas AV & McDonnell ME. 2018. Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinol Metab Clin North Am. 47(1): 51–63.
Henriksen EJ, Jacob S. 2003. Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol. 196(1): 171–179.
Hunyady L, Catt KJ. 2006. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 20(5): 953–970.
Ilatovskaya DV, Levchenko V, Lowing A, Shuyskiy LS, Palygin O, Staruschenko A. 2015. Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. Sci Rep. 5, 17637.
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Kass DA. 2003. Getting better without AGE: new insights into the diabetic heart. Circ Res. 92(7): 704–706.
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. Nutr diabetes. 9(1): 9.
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Leung SS, Forbes JM, Borg DJ. 2016. Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis. Curr Diab Rep. 16(10): 100.
Lim S, Lee ME, Jeong J, Lee J, Cho S, Seo M, Park S. 2018. sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation. Inflamm Res. 67(8): 691–701.
Lozano-Maneiro L, Puente-García A. 2015. Renin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences. J Clin Med. 4(11): 1908–1937.
McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, Bild DE, Shea S, Liu K, Watson KE, et al. 2015. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 66(15): 1643–1653.
Miller, AJ, Arnold, AC. (2019). The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clin Auton Res. 29(2), 231–243.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després, JP, Fullerton HJ, Howard V, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 2015. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 131(4): e29–e322.
Muñoz M, Rincón J, Pedreañez A, Viera N, Hernández-Fonseca JP, Mosquera J. 2011. Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin. J Renin Angiotensin Aldosterone Syst. 12(4): 404–412.
Ogata Y, Nemoto W, Nakagawasai O, Yamagata R, Tadano T, Tan-No K. 2016. Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice. Mol Pharmacol. 90(3): 205–213.
Orea-Tejeda A, Colín-Ramírez E, Castillo-Martínez L, Asensio-Lafuente E, Corzo-León D, González- Toledo R, Rebollar-González V, Narváez-David R, & Dorantes-García J. 2007. Aldosterone receptor antagonists induce favorable cardiac remodeling in diastolic heart failure patients. Rev Invest Clin. 59(2): 103–107.
Pickering RJ, Tikellis C, Rosado CJ, Tsorotes D, Dimitropoulos A, Smith M, Huet O, Seeber R M, Abhayawardana R, Johnstone EK, et al. 2019. Transactivation of RAGE mediates angiotensin- induced inflammation and atherogenesis. J Clin Invest. 129(1): 406–421.
Qian X, Lin L, Zong Y, Yuan Y, Dong Y, Fu Y, Shao W, Li Y, Gao Q. 2018. Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice. Graefes Arch Clin Exp Ophthalmol. 256(3): 525–534.
Roscioni SS, Heerspink HJ, de Zeeuw D. 2014. The effect of RAAS blockade on the progression of diabetic nephropathy. Nat Rev Nephrol. 10(2): 77–87.
Scheen AJ. 2004. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab. 30(6): 498–505.
Schievink B, Kröpelin T, Mulder S, Parving HH, Remuzzi G, Dwyer J, Vemer P, de Zeeuw D, Lambers Heerspink HJ. 2016. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes. Diabetes Obes Metab. 18(1): 64–71.
Singh VP, Le B, Khode R, Baker KM, Kumar R. 2008. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes. 57(12): 3297–3306.
Smith DH. 2008. Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. Drugs. 68(9): 1207–1225.
Stefano GB, Challenger S, Kream RM. 2016. Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. Eur J Nutr. 55(8): 2339–2345.
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. Urata H, Boehm KD, Philip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A. 1993. Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest. 91(4): 1269–1281.
Urata H, Kinoshita A, Perez DM, Misono KS, Bumpus FM, Graham RM, Husain A. 1991. Cloning of the gene and cDNA for human heart chymase. J Biol Chem. 266(26): 17173–17179.
Vargas R, Rincón J, Pedreañez A, Viera N, Hernández-Fonseca JP, Peña C, & Mosquera J. 2012. Role of angiotensin II in the brain inflammatory events during experimental diabetes in rats. Brain Res. 1453: 64–76.
Varma U, Koutsifeli P, Benson VL, Mellor KM, Delbridge L. 2018. Molecular mechanisms of cardiac pathology in diabetes - Experimental insights. Biochim Biophys Acta Mol Basis Dis. 1864(5 Pt B): 1949–1959.
Wang X, Ye Y, Gong H, Wu J, Yuan J, Wang S, Yin P, Ding Z, Kang L, Jiang Q, et al. 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. J Mol Cell Cardiol. 97: 180–190.
Westermann D, Rutschow S, Jäger S, Linderer A, Anker S, Riad A, UngerT, Schultheiss HP, Pauschinger M, Tschöpe C. 2007. Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. Diabetes. 56(3): 641–646.
Zhou J, Xu X, Liu JJ, Lin YX, Gao GD. 2007. Angiotensin II receptors subtypes mediate diverse gene expression profile in adult hypertrophic cardiomyocytes. Clin Exp Pharmacol Physiol. 34(11): 1191–1198.
Bugger H, Abel ED. 2014. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 57(4): 660–671.
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. Oxid Med Cell Longev. 2018: 8616194.
Chen CM, Juan SH, Chou HC. 2018. Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys. Journal of the renin-angiotensin-aldosterone system : J Renin Angiotensin Aldosterone Syst. 19(3): 1470320318803009.
El Desoky ES. 2011. Drug therapy of heart failure: an immunologic view. Am J Ther. 18(5): 416–425.
Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. 2014. Therapeutic approaches to diabetic nephropathy--beyond the RAS. Nat Rev Nephro. 10(6): 325–346.
Goldin A, Beckman JA, Schmidt AM, Creager MA. 2006. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 114(6): 597–605.
Haas AV & McDonnell ME. 2018. Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinol Metab Clin North Am. 47(1): 51–63.
Henriksen EJ, Jacob S. 2003. Modulation of metabolic control by angiotensin converting enzyme (ACE) inhibition. J Cell Physiol. 196(1): 171–179.
Hunyady L, Catt KJ. 2006. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 20(5): 953–970.
Ilatovskaya DV, Levchenko V, Lowing A, Shuyskiy LS, Palygin O, Staruschenko A. 2015. Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. Sci Rep. 5, 17637.
Jing YH, Chen KH, Yang, SH, Kuo, PC, Chen, JK. 2010. Resveratrol ameliorates vasculopathy in STZ- induced diabetic rats: role of AGE-RAGE signalling. Diabetes Metab Res Re. 26(3): 212–222.
Kass DA. 2003. Getting better without AGE: new insights into the diabetic heart. Circ Res. 92(7): 704–706.
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. Nutr diabetes. 9(1): 9.
Kinoshita A, Urata H, Bumpus FM, Husain A. 1991. Multiple determinants for the high substrate specificity of an angiotensin II-forming chymase from the human heart. J Biol Chem. 266(29): 19192–19197.
Leung SS, Forbes JM, Borg DJ. 2016. Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis. Curr Diab Rep. 16(10): 100.
Lim S, Lee ME, Jeong J, Lee J, Cho S, Seo M, Park S. 2018. sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation. Inflamm Res. 67(8): 691–701.
Lozano-Maneiro L, Puente-García A. 2015. Renin-Angiotensin-Aldosterone System Blockade in Diabetic Nephropathy. Present Evidences. J Clin Med. 4(11): 1908–1937.
McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, Bild DE, Shea S, Liu K, Watson KE, et al. 2015. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 66(15): 1643–1653.
Miller, AJ, Arnold, AC. (2019). The renin-angiotensin system in cardiovascular autonomic control: recent developments and clinical implications. Clin Auton Res. 29(2), 231–243.
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Després, JP, Fullerton HJ, Howard V, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 2015. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 131(4): e29–e322.
Muñoz M, Rincón J, Pedreañez A, Viera N, Hernández-Fonseca JP, Mosquera J. 2011. Proinflammatory role of angiotensin II in a rat nephrosis model induced by adriamycin. J Renin Angiotensin Aldosterone Syst. 12(4): 404–412.
Ogata Y, Nemoto W, Nakagawasai O, Yamagata R, Tadano T, Tan-No K. 2016. Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice. Mol Pharmacol. 90(3): 205–213.
Orea-Tejeda A, Colín-Ramírez E, Castillo-Martínez L, Asensio-Lafuente E, Corzo-León D, González- Toledo R, Rebollar-González V, Narváez-David R, & Dorantes-García J. 2007. Aldosterone receptor antagonists induce favorable cardiac remodeling in diastolic heart failure patients. Rev Invest Clin. 59(2): 103–107.
Pickering RJ, Tikellis C, Rosado CJ, Tsorotes D, Dimitropoulos A, Smith M, Huet O, Seeber R M, Abhayawardana R, Johnstone EK, et al. 2019. Transactivation of RAGE mediates angiotensin- induced inflammation and atherogenesis. J Clin Invest. 129(1): 406–421.
Qian X, Lin L, Zong Y, Yuan Y, Dong Y, Fu Y, Shao W, Li Y, Gao Q. 2018. Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice. Graefes Arch Clin Exp Ophthalmol. 256(3): 525–534.
Roscioni SS, Heerspink HJ, de Zeeuw D. 2014. The effect of RAAS blockade on the progression of diabetic nephropathy. Nat Rev Nephrol. 10(2): 77–87.
Scheen AJ. 2004. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab. 30(6): 498–505.
Schievink B, Kröpelin T, Mulder S, Parving HH, Remuzzi G, Dwyer J, Vemer P, de Zeeuw D, Lambers Heerspink HJ. 2016. Early renin-angiotensin system intervention is more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes. Diabetes Obes Metab. 18(1): 64–71.
Singh VP, Le B, Khode R, Baker KM, Kumar R. 2008. Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis. Diabetes. 57(12): 3297–3306.
Smith DH. 2008. Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. Drugs. 68(9): 1207–1225.
Stefano GB, Challenger S, Kream RM. 2016. Hyperglycemia-associated alterations in cellular signaling and dysregulated mitochondrial bioenergetics in human metabolic disorders. Eur J Nutr. 55(8): 2339–2345.
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. Urata H, Boehm KD, Philip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A. 1993. Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest. 91(4): 1269–1281.
Urata H, Kinoshita A, Perez DM, Misono KS, Bumpus FM, Graham RM, Husain A. 1991. Cloning of the gene and cDNA for human heart chymase. J Biol Chem. 266(26): 17173–17179.
Vargas R, Rincón J, Pedreañez A, Viera N, Hernández-Fonseca JP, Peña C, & Mosquera J. 2012. Role of angiotensin II in the brain inflammatory events during experimental diabetes in rats. Brain Res. 1453: 64–76.
Varma U, Koutsifeli P, Benson VL, Mellor KM, Delbridge L. 2018. Molecular mechanisms of cardiac pathology in diabetes - Experimental insights. Biochim Biophys Acta Mol Basis Dis. 1864(5 Pt B): 1949–1959.
Wang X, Ye Y, Gong H, Wu J, Yuan J, Wang S, Yin P, Ding Z, Kang L, Jiang Q, et al. 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. J Mol Cell Cardiol. 97: 180–190.
Westermann D, Rutschow S, Jäger S, Linderer A, Anker S, Riad A, UngerT, Schultheiss HP, Pauschinger M, Tschöpe C. 2007. Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism. Diabetes. 56(3): 641–646.
Zhou J, Xu X, Liu JJ, Lin YX, Gao GD. 2007. Angiotensin II receptors subtypes mediate diverse gene expression profile in adult hypertrophic cardiomyocytes. Clin Exp Pharmacol Physiol. 34(11): 1191–1198.