Skip to main content
SpringerLink
Log in

Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions

  • Review
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. The presence and accumulation of AGEs in various cardiac cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-κB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE-induced mitochondrial dysfunction in the myocardium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Poulsen M.W., Hedegaard R.V., Andersen J.M., de Courten B., Bügel S., Nielsen J., et al.: Advanced glycation endproducts in food and their effects on health. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc. 60, 10–37 (2013)

    Article  CAS  Google Scholar 

  2. Ott C., Jacobs K., Haucke E., Navarrete Santos A., Grune T., Simm A.: Role of advanced glycation end products in cellular signaling. Redox Biol. 2, 411–429 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Boulanger E., Wautier M.P., Wautier J.L., Boval B., Panis Y., Wernert N., Danze P.M., Dequiedt P.: AGEs bind to mesothelial cells via RAGE and stimulate VCAM-1 expression. Kidney Int. 61, 148–156 (2002)

    Article  CAS  PubMed  Google Scholar 

  4. Boulanger E., Grossin N., Wautier M.P., Taamma R., Wautier J.L.: Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation. Kidney Int. 71, 126–133 (2007)

    Article  CAS  PubMed  Google Scholar 

  5. Daroux M, Prévost G, Maillard-Lefebvre H, Gaxatte C, D’Agati VD, Schmidt AM, Boulanger E.: Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabete Metab. 36, 1–10 (2010)

  6. Zhao J., Randive R., Stewart J.A.: Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart. World J. Diabetes. 6, 860–867 (2014)

    Article  Google Scholar 

  7. Ramasamy R., Schmidt A.M.: Receptor for advanced glycation end products (RAGE) and implications for the pathophysiology of heart failure. Curr. Heart Fail. Rep. 2, 107–116 (2012)

    Article  Google Scholar 

  8. Barlovic D.P., Soro-Paavonen A., Jandeleit-Dahm K.A.M.: RAGE biology, atherosclerosis and diabetes. Clin. Sci. Lond. Engl. 121, 43–55 (2011)

    Article  CAS  Google Scholar 

  9. Bucciarelli L.G., Ananthakrishnan R., Hwang Y.C., Kaneko M., Song F., Sell D.R., et al.: RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes. 57, 1941–1951 (2004)

    Article  Google Scholar 

  10. Bucciarelli L.G., Kaneko M., Ananthakrishnan R., Harja E., Lee L.K., Hwang Y.C., et al.: Receptor for advanced-glycation end products: key modulator of myocardial ischemic injury. Circulation. 113, 1226–1234 (2006)

    Article  CAS  PubMed  Google Scholar 

  11. Shang L., Ananthakrishnan R., Li Q., Quadri N., Abdillahi M., Zhu Z., et al.: RAGE modulates hypoxia/reoxygenation injury in adult murine cardiomyocytes via JNK and GSK-3beta signaling pathways. PLoS ONE. 4, e10092 (2010)

    Article  Google Scholar 

  12. Nielsen J.M., Kristiansen S.B., Nørregaard R., Andersen C.L., Denner L., Nielsen T.T., et al.: Blockage of receptor for advanced glycation end products prevents development of cardiac dysfunction in db/db type 2 diabetic mice. Eur. J. Heart Fail. 11, 638–647 (2009)

    Article  CAS  PubMed  Google Scholar 

  13. Fukami K., Yamagishi S.-I., Okuda S.: Role of AGEs-RAGE system in cardiovascular disease. Curr. Pharm. Des. 20, 2395–2402 (2014)

    Article  CAS  PubMed  Google Scholar 

  14. Schmidt A.M.: Soluble RAGEs - Prospects for treating & tracking metabolic and inflammatory disease. Vasc. Pharmacol. 72, 1–8 (2015)

    Article  CAS  Google Scholar 

  15. Yamagishi S., Matsui T.: NakamuraK.: Kinetics, role and therapeutic implications of endogenous soluble form of receptor for advanced glycation end products (sRAGE) in diabetes. Curr. Drug Targets. 8, 1138–1143 (2007)

    Article  CAS  Google Scholar 

  16. Raucci A., Cugusi S., Antonelli A., Barabino S.M., Monti L., Bierhaus A., et al.: A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J. 22, 3716–3727 (2008)

    Article  CAS  PubMed  Google Scholar 

  17. Koyama Y., Takeishi Y., Niizeki T., Suzuki S., Kitahara T., Sasaki T., Kubota I.: Soluble Receptor for advanced glycation end products (RAGE) is a prognostic factor for heart failure. J. Card. Fail. 14, 133–139 (2008)

    Article  CAS  PubMed  Google Scholar 

  18. Bucciarelli L.G., Wendt T., Qu W., Lu Y., Lalla E., Rong L.L., Goova M.T., Moser B., Kislinger T., Lee D.C., Kashyap Y., Stern D.M., Schmidt A.M.: RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice. Circulation. 106, 2827–2835 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. Nakamura K., Adachi H., Matsui T., Kurita Y., Takeuchi M., Yamagishi S.: Independent determinants of soluble form of receptor for advanced glycation end products in elderly hypertensive patients. Metabolism. 58, 421–425 (2009)

    Article  CAS  PubMed  Google Scholar 

  20. Nakamura K., Yamagishi S., Nakamura Y., Takenaka K., Matsui T., Jinnouchi Y., Imaizumi T.: Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc. Res. 70, 137–141 (2005)

    Article  CAS  PubMed  Google Scholar 

  21. Geroldi D, Falcone C, Emanuele E, D’Angelo A, Calcagnino M, Buzzi MP, Scioli GA, Fogari R.: Decreased plasma levels of soluble receptor for advanced glycation end-products in patients with essential hypertension. J. Hypertens. 23, 1725–1729 (2005)

  22. Falcone C, Emanuele E, D’Angelo A, Buzzi MP, Belvito C, Cuccia M, Geroldi D.: Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler. Thromb. Vasc. Biol. 25, 1032–1037 (2005)

  23. Mahajan N., Malik N., Bahl A., Dhawan V.: Receptor for advanced glycation end products (RAGE) and its inflammatory ligand EN-RAGE in non-diabetic subjects with pre-mature coronary artery disease. Atherosclerosis. 207(2), 597–602 (2009)

    Article  CAS  PubMed  Google Scholar 

  24. Mulder D.J., van Haelst P.L., Gross S., de Leeuw K., Bijzet J., Graaff R., et al.: Skin autofluorescence is elevated in patients with stable coronary artery disease and is associated with serum levels of neopterin and the soluble receptor for advanced glycation end products. Atherosclerosis. 197, 217–223 (2008)

    Article  CAS  PubMed  Google Scholar 

  25. Raposeiras-Roubín S., Rodiño-Janeiro B.K., Grigorian-Shamagian L., Moure-González M., Seoane-Blanco A., Varela-Román A., et al.: Relation of soluble receptor for advanced glycation end products to predict mortality in patients with chronic heart failure independently of Seattle Heart Failure Score. Am. J. Cardiol. 107, 938–944 (2011)

    Article  PubMed  Google Scholar 

  26. Raposeiras-Roubín S., Rodiño-Janeiro B.K., Grigorian-Shamagian L., Moure-González M., Seoane-Blanco A., Varela-Román A., et al.: Soluble receptor of advanced glycation end products levels are related to ischaemic aetiology and extent of coronary disease in chronic heart failure patients, independent of advanced glycation end products levels: New Roles for Soluble RAGE. Eur. J. Heart Fail. 12, 1092–1100 (2010)

    Article  PubMed  Google Scholar 

  27. Raposeiras-Roubín S., Rodiño-Janeiro B.K., Grigorian-Shamagian L., Seoane-Blanco A., Moure-González M., Varela-Román A., et al.: Evidence for a role of advanced glycation end products in atrial fibrillation. Int. J. Cardiol. 157, 397–402 (2012)

    Article  PubMed  Google Scholar 

  28. Basta G., Leonardis D., Mallamaci F., Cutrupi S., Pizzini P., Gaetano L., et al.: Circulating soluble receptor of advanced glycation end product inversely correlates with atherosclerosis in patients with chronic kidney disease. Kidney Int. 77, 225–231 (2010)

    Article  CAS  PubMed  Google Scholar 

  29. Kim J.K., Park S., Lee M.J., Song Y.R., Han S.H., Kim S.G., et al.: Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis. Atherosclerosis. 220, 208–214 (2012)

    Article  CAS  PubMed  Google Scholar 

  30. Leonardis D., Basta G., Mallamaci F., Cutrupi S., Pizzini P., Tripepi R., Tripepi G., De Caterina R., Zoccali C., et al.: Circulating soluble receptor for advanced glycation end product (sRAGE) and left ventricular hypertrophy in patients with chronic kidney disease (CKD). Nutr. Metab. Cardiovasc. Dis. 22, 748–755 (2012)

    Article  CAS  PubMed  Google Scholar 

  31. Prasad K.: Low levels of serum soluble receptors for advanced glycation end products, biomarkers for disease state: myth or reality. Int. J. Angiol. 23, 11–16 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  32. Selvin E., Halushka M.K., Rawlings A.M., Hoogeveen R.C., Ballantyne C.M., Coresh J., et al.: sRAGE and risk of diabetes, cardiovascular disease, and death. Diabetes. 62, 2116–2121 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yan S.F., Ramasamy R., Schmidt A.M.: The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ. Res. Mar. 106, 842–853 (2010)

    Article  CAS  Google Scholar 

  34. Brett J., Schmidt A.M., Yan S.D., Zou Y.S., Weidman E., Pinsky D., et al.: Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am. J. Pathol. 143, 1699–1712 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Donaldson C., Taatjes D.J., Zile M., Palmer B., VanBuren P., Spinale F., et al.: Combined immunoelectron microscopic and computer-assisted image analyses to detect advanced glycation end-products in human myocardium. Histochem. Cell Biol. 134, 23–30 (2010)

    Article  CAS  PubMed  Google Scholar 

  36. Willemsen S., Hartog J.W.L., Heiner-Fokkema M.R., van Veldhuisen D.J., Voors A.A.: Advanced glycation end-products, a pathophysiological pathway in the cardiorenal syndrome. Heart Fail. Rev. 17, 221–228 (2012)

    Article  CAS  PubMed  Google Scholar 

  37. Smit A.J., Hartog J.W.L., Voors A.A., van Veldhuisen D.J.: Advanced glycation endproducts in chronic heart failure. Ann. N. Y. Acad. Sci. 1126, 225–230 (2008)

    Article  CAS  PubMed  Google Scholar 

  38. Hartog J.W.L., Voors A.A., Bakker S.J.L., Smit A.J., van Veldhuisen D.J.: Advanced glycation end-products (AGEs) and heart failure: pathophysiology and clinical implications. Eur. J. Heart Fail. 9, 1146–1155 (2007)

    Article  CAS  PubMed  Google Scholar 

  39. Campbell D.J., Somaratne J.B., Jenkins A.J., Prior D.L., Yii M., Kenny J.F., et al.: Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease. Cardiovasc. Diabetol. 10, 80–86 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nożyński J., Zakliczyński M., Konecka-Mrowka D., Zielinska T., Zakliczynska H., Nikiel B., et al.: Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes. Ann. Transplant. Q. Pol. Transplant. Soc. 17, 53–61 (2012)

    Google Scholar 

  41. Nenna A., Nappi F., Avtaar Singh S.S., Sutherland F.W., Di Domenico F., Chello M., Spadaccio C.: Pharmacologic Approaches Against Advanced Glycation End Products (AGEs) in Diabetic Cardiovascular Disease. Res. Cardiovasc. Med. 4, e26949 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  42. Engelen L., Stehouwer C.D., Schalkwijk C.G.: Current therapeutic interventions in the glycation pathway: evidence from clinical studies. Diabetes Obes. Metab. 15, 677–689 (2013)

    Article  CAS  PubMed  Google Scholar 

  43. Bolton W.K., Cattran D.C., Williams M.E., Adler S.G., Appel G.B., Cartwright K., Foiles P.G., Freedman B.I., Raskin P., Ratner R.E., Spinowitz B.S., Whittier F.C., Wuerth J.P., ACTION I Investigator Group., et al.: Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am. J. Nephrol. 24, 32–40 (2004)

    Article  CAS  PubMed  Google Scholar 

  44. Kass D.A., Shapiro E.P., Kawaguchi M., Capriotti A.R., Scuteri A.: deGroof RC, Lakatta EG.: Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation. 104, 1464–1470 (2001)

    Article  CAS  PubMed  Google Scholar 

  45. Hartog J.W.L., Willemsen S., van Veldhuisen D.J., Posma J.L., van Wijk L.M., Hummel Y.M., et al.: Effects of alagebrium, an advanced glycation endproduct breaker, on exercise tolerance and cardiac function in patients with chronic heart failure. Eur. J. Heart Fail. 13, 899–908 (2011)

    Article  CAS  PubMed  Google Scholar 

  46. Zieman S.J., Melenovsky V., Clattenburg L., Corretti M.C., Capriotti A., Gerstenblith G., et al.: Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J. Hypertens. 25, 577–583 (2007)

    Article  CAS  PubMed  Google Scholar 

  47. Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien TX, Degroof RC.: The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J. Card. Fail. 11, 191–195 (2005)

  48. Willemsen S., Hartog J.W., Hummel Y.M., Posma J.L., van Wijk L.M., van Veldhuisen D.J., Voors A.A.: Effects of alagebrium, an advanced glycation end-product breaker, in patients with chronic heart failure: study design and baseline characteristics of the BENEFICIAL trial. Eur. J. Heart Fail. 12, 294–300 (2010)

    Article  CAS  PubMed  Google Scholar 

  49. Fujimoto N., Hastings J.L., Carrick-Ranson G., Shafer K.M., Shibata S., Bhella P.S., et al.: Cardiovascular effects of 1 year of alagebrium and endurance exercise training in healthy older individuals. Circ. Heart Fail. 6, 1155–1164 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Uribarri J., Woodruff S., Goodman S., Cai W., Chen X., Pyzik R., et al.: Advanced glycation end products in foods and a practical guide to their reduction in the diet. J. Am. Diet. Assoc. 110, 911–916 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  51. Koschinsky T., He C.J., Mitsuhashi T., Bucala R., Liu C., Buenting C., et al.: Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc. Natl. Acad. Sci. U. S. A. 94, 6474–6479 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yamagishi S.-I., Matsui T.: Pathologic role of dietary advanced glycation end products in cardiometabolic disorders, and therapeutic intervention. Nutrition. 32, 157–165 (2016)

    Article  CAS  PubMed  Google Scholar 

  53. Clarke R.E., Dordevic A.L., Tan S.M., Ryan L., Coughlan M.T.: Dietary Advanced Glycation End Products and Risk Factors for Chronic Disease: A Systematic Review of Randomised Controlled Trials. Nutrients. 8, E125 (2016)

    Article  PubMed  Google Scholar 

  54. Stirban A., Gawlowski T., Roden M.: Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms. Mol. Metab. 3, 94–108 (2014)

    Article  CAS  PubMed  Google Scholar 

  55. Grossin N., Auger F., Niquet-Leridon C., Durieux N., Montaigne D., Schmidt A.M., et al.: Dietary CML-enriched protein induces functional arterial aging in a RAGE-dependent manner in mice. Mol. Nutr. Food Res. 59, 927–938 (2015)

    Article  CAS  PubMed  Google Scholar 

  56. Uribarri J., Stirban A., Sander D., Cai W., Negrean M., Buenting C.E., et al.: Single oral challenge by advanced glycation end products acutely impairs endothelial function in diabetic and nondiabetic subjects. Diabetes Care. 30, 2579–2582 (2007)

    Article  CAS  PubMed  Google Scholar 

  57. Lin R.Y., Reis E.D., Dore A.T., Lu M., Ghodsi N., Fallon J.T., et al.: Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal formation after arterial injury in genetically hypercholesterolemic mice. Atherosclerosis. 163, 303–311 (2002)

    Article  CAS  PubMed  Google Scholar 

  58. Lin R.Y., Choudhury R.P., Cai W., Lu M., Fallon J.T., Fisher E.A., Vlassara H.: Dietary glycotoxins promote diabetic atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis. 168, 213–220 (2003)

    Article  CAS  PubMed  Google Scholar 

  59. Chen S.X., Song T., Zhou S.H., Liu Y.H., Wu S.J., Liu L.Y.: Protective effects of ACE inhibitors on vascular endothelial dysfunction induced by exogenous advanced oxidation protein products in rats. Eur. J. Pharmacol. 584, 368–375 (2008)

    Article  CAS  PubMed  Google Scholar 

  60. Semba R.D., Gebauer S.K., Baer D.J., Sun K., Turner R., Silber H.A., Taleqawkar S., Ferrucci L., Novotny J.A., et al.: Dietary intake of advanced glycation end products did not affect endothelial function and inflammation in healthy adults in a randomized controlled trial. J. Nutr. 144, 1037–1042 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Semba R.D., Ang A., Talegawkar S., Crasto C., Dalal M., Jardack P., Traber M.G., Ferrucci L., Arab L., et al.: Dietary intake associated with serum versus urinary carboxymethyl-lysine, a major advanced glycation end product, in adults: the Energetics Study. Eur. J. Clin. Nutr. 66, 3–9 (2012)

    Article  CAS  PubMed  Google Scholar 

  62. Chen X., Mori T., Guo Q., Hu C., Ohsaki Y., Yoneki Y., et al.: Carbonyl stress induces hypertension and cardio–renal vascular injury in Dahl salt-sensitive rats. Hypertens. Res. 36, 361–367 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Crisóstomo J., Matafome P., Santos-Silva D., Rodrigues L., Sena C.M., Pereira P., et al.: Methylglyoxal chronic administration promotes diabetes-like cardiac ischaemia disease in Wistar normal rats. Nutr. Metab. Cardiovasc. Dis. 23, 1223–1230 (2013)

    Article  PubMed  Google Scholar 

  64. Kellow N.J., Savige G.S.: Dietary advanced glycation end-product restriction for the attenuation of insulin resistance, oxidative stress and endothelial dysfunction: a systematic review. Eur. J. Clin. Nutr. 67, 239–248 (2013)

    Article  CAS  PubMed  Google Scholar 

  65. Asif M., Egan J., Vasan S., Jyothirmayi G.N., Masurekar M.R., Lopez S., et al.: An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc. Natl. Acad. Sci. U. S. A. 97, 2809–2813 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. van Heerebeek L., Hamdani N., Handoko M.L., Falcao-Pires I., Musters R.J., Kupreishvili K., et al.: Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 117, 43–51 (2008)

    Article  PubMed  Google Scholar 

  67. Aronson D.: Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J. Hypertens. 21, 3–12 (2003)

    Article  CAS  PubMed  Google Scholar 

  68. Bucala R., Tracey K.J., Cerami A.: Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J. Clin. Invest. 87, 432–438 (1991)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Su J., Lucchesi P.A., Gonzalez-Villalobos R.A., Palen D.I., Rezk B.M., Suzuki Y., et al.: Role of advanced glycation end products with oxidative stress in resistance artery dysfunction in type 2 diabetic mice. Arterioscler. Thromb. Vasc. Biol. 28, 1432–1438 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sena C.M., Matafome P., Crisóstomo J., Rodrigues L., Fernandes R., Pereira P., et al.: Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol. Res. 65, 497–506 (2012)

    Article  CAS  PubMed  Google Scholar 

  71. Xu B., Ji Y., Yao K., Cao Y.-X., Ferro A.: Inhibition of human endothelial cell nitric oxide synthesis by advanced glycation end-products but not glucose: relevance to diabetes. Clin. Sci. Lond. Engl. 109, 439–446 (2005)

    Article  CAS  Google Scholar 

  72. Xu B., Chibber R., Ruggiero D., Kohner E., Ritter J., Ferro A., et al.: Impairment of vascular endothelial nitric oxide synthase activity by advanced glycation end products. FASEB J. 17, 1289–1291 (2003)

    Article  CAS  PubMed  Google Scholar 

  73. Prasad K., Dhar I., Caspar-Bell G.: Role of Advanced Glycation End Products and Its Receptors in the Pathogenesis of Cigarette Smoke-Induced Cardiovascular Disease. Int. J. Angiol. 24, 75–80 (2015)

    PubMed  Google Scholar 

  74. Russo I., Frangogiannis N.G.: Diabetes-associated cardiac fibrosis: Cellular effectors, molecular mechanisms and therapeutic opportunities. J. Mol. Cell. Cardiol. 90, 84–93 (2015)

    Article  PubMed  Google Scholar 

  75. Thallas-Bonke V., Coughlan M.T., Tan A.L., Harcourt B.E., Morgan P.E., Davies M.J., et al.: Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content. Nephrol. Carlton Vic. 18, 47–56 (2013)

    Article  CAS  Google Scholar 

  76. Petrova R., Yamamoto Y., Muraki K., Yonekura H., Sakurai S., Watanabe T., et al.: Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes. J. Mol. Cell. Cardiol. 34, 1425–1431 (2002)

    Article  CAS  PubMed  Google Scholar 

  77. Yan D., Luo X., Li Y., Liu W., Deng J., Zheng N., et al.: Effects of advanced glycation end products on calcium handling in cardiomyocytes. Cardiology. 129, 75–83 (2014)

    Article  CAS  PubMed  Google Scholar 

  78. Ma H., Li S.-Y., Xu P., Babcock S.A., Dolence E.K., Brownlee M., et al.: Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up-regulation contribute to the onset of diabetic cardiomyopathy. J. Cell. Mol. Med. 13, 1751–1764 (2009)

    Article  PubMed  Google Scholar 

  79. Yuan Q., Zhou Q.-Y., Liu D., Yu L., Zhan L., Li X.-J., et al.: Advanced glycation end-products impair Na+/K+-ATPase activity in diabetic cardiomyopathy: role of the adenosine monophosphate-activated protein kinase/sirtuin 1 pathway. Clin. Exp. Pharmacol. Physiol. 41, 127–133 (2014)

    Article  CAS  PubMed  Google Scholar 

  80. Rojas A., Mercadal E., Figueroa H., Morales M.A.: Advanced Glycation and ROS: a link between diabetes and heart failure. Curr. Vasc. Pharmacol. 6, 44–51 (2008)

    Article  CAS  PubMed  Google Scholar 

  81. Li S.-Y., Sigmon V.K., Babcock S.A., Ren J.: Advanced glycation endproduct induces ROS accumulation, apoptosis, MAP kinase activation and nuclear O-GlcNAcylation in human cardiac myocytes. Life Sci. 80, 1051–1056 (2007)

    Article  CAS  PubMed  Google Scholar 

  82. Ward M.S., Fortheringham A.K., Cooper M.E., Forbes J.M.: Targeting advanced glycation endproducts and mitochondrial dysfunction in cardiovascular disease. Curr. Opin. Pharmacol. 13, 654–661 (2013)

    Article  CAS  PubMed  Google Scholar 

  83. Daffu G., del Pozo C.H., O’Shea K.M., Ananthakrishnan R., Ramasamy R., Schmidt A.M.: Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular diseases and beyond. Int. J. Mol. Sci. 14, 19,891–19,910 (2013)

    Article  Google Scholar 

  84. Wang L., Li Q., Du J., Chen B., Li Q., Huang X., et al.: Advanced glycation end products induce moesin phosphorylation in murine retinal endothelium. Acta Diabetol. 49, 47–55 (2012)

    Article  CAS  PubMed  Google Scholar 

  85. Diguet N., Mallat Y., Ladouce R., Clodic G., Prola A., Tritsch E., et al.: Muscle creatine kinase deficiency triggers both actin depolymerization and desmin disorganization by advanced glycation end products in dilated cardiomyopathy. J. Biol. Chem. 286, 35,007–35,019 (2011)

    Article  CAS  Google Scholar 

  86. Li Z., Zhong Q., Yang T., Xie X., Chen M.: The role of profilin-1 in endothelial cell injury induced by advanced glycation end products (AGEs). Cardiovasc. Diabetol. 12, 141 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  87. Xie J., Méndez J.D., Méndez-Valenzuela V., Aguilar-Hernández M.M.: Cellular signalling of the receptor for advanced glycation end products (RAGE). Cell. Signal. 25, 2185–2197 (2013)

    Article  CAS  PubMed  Google Scholar 

  88. Tsoporis J.N., Izhar S., Leong-Poi H., Desjardins J.-F., Huttunen H.J., Parker T.G.: S100B interaction with the receptor for advanced glycation end products (RAGE): a novel receptor-mediated mechanism for myocyte apoptosis postinfarction. Circ. Res. 106, 93–101 (2010)

    Article  CAS  PubMed  Google Scholar 

  89. Guo C., Zeng X., Song J., Zhang M., Wang H., Xu X., et al.: A soluble receptor for advanced glycation end-products inhibits hypoxia/reoxygenation-induced apoptosis in rat cardiomyocytes via the mitochondrial pathway. Int. J. Mol. Sci. 13, 11,923–11,940 (2012)

    Article  CAS  Google Scholar 

  90. Jiang X., Guo C., Zeng X., Li H., Chen B., Du F.: A soluble receptor for advanced glycation end-products inhibits myocardial apoptosis induced by ischemia/reperfusion via the JAK2/STAT3 pathway. Apoptosis Int. J. Program. Cell. Death. 20, 1033–1047 (2015)

    Article  CAS  Google Scholar 

  91. Kang R., Tang D., Schapiro N.E., Livesey K.M., Farkas A., Loughran P., et al.: The receptor for advanced glycation end products (RAGE) sustains autophagy and limits apoptosis, promoting pancreatic tumor cell survival. Cell Death Differ. 17, 666–676 (2010)

    Article  CAS  PubMed  Google Scholar 

  92. Hou X., Hu Z., Xu H., Xu J., Zhang S., Zhong Y., et al.: Advanced glycation endproducts trigger autophagy in cadiomyocyte via RAGE/PI3K/AKT/mTOR pathway. Cardiovasc. Diabetol. 13, 78 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  93. Hu P., Zhou H., Lu M., Dou L., Bo G., Wu J., et al.: Autophagy Plays a Protective Role in Advanced Glycation End Product-Induced Apoptosis in Cardiomyocytes. Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol. 37, 697–706 (2015)

    Article  CAS  Google Scholar 

  94. Nelson M.B., Swensen A.C., Winden D.R., Bodine J.S., Bikman B.T., Reynolds P.R.: Cardiomyocyte mitochondrial respiration is reduced by receptor for advanced glycation end-product signaling in a ceramide-dependent manner. Am. J. Physiol. Heart Circ. Physiol. 309, H63–H69 (2015)

    Article  CAS  PubMed  Google Scholar 

  95. Bakala H., Hamelin M., Mary J., Borot-Laloi C., Friguet B.: Catalase, a target of glycation damage in rat liver mitochondria with aging. Biochim. Biophys. Acta. 1822, 1527–1534 (2012)

    Article  CAS  PubMed  Google Scholar 

  96. Bakala H., Ladouce R., Baraibar M.A., Friguet B.: Differential expression and glycative damage affect specific mitochondrial proteins with aging in rat liver. Biochim. Biophys. Acta. 1832, 2057–2067 (2013)

    Article  CAS  PubMed  Google Scholar 

  97. Cai W., Ramdas M., Zhu L., Chen X., Striker G.E., Vlassara H.: Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1. Proc. Natl. Acad. Sci. U. S. A. 109, 15,888–15,893 (2012)

    Article  CAS  Google Scholar 

  98. Cai W., Uribarri J., Zhu L., Chen X., Swamy S., Zhao Z., et al.: Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc. Natl. Acad. Sci. U. S. A. 111, 4940–4945 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Huang K.-P., Chen C., Hao J., Huang J.-Y., Liu P.-Q., Huang H.-Q.: AGEs-RAGE system down-regulates Sirt1 through the ubiquitin-proteasome pathway to promote FN and TGF-β1 expression in male rat glomerular mesangial cells. Endocrinology. 156, 268–279 (2015)

    Article  PubMed  Google Scholar 

  100. Yu T., Jhun B.S., Yoon Y.: High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxid. Redox Signal. 14, 425–437 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Lo M.-C., Chen M.-H., Lee W.-S., Lu C.-I., Chang C.-R., Kao S.-H., et al.: Nε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells. Am. J. Physiol. Endocrinol. Metab. 309, E829–E839 (2015)

    CAS  PubMed  Google Scholar 

  102. Dorn G.W.: Mitochondrial dynamism and heart disease: changing shape and shaping change. EMBO Mol. Med. 7, 865–877 (2015)

    Article  CAS  PubMed  Google Scholar 

  103. Hoshino A., Ariyoshi M., Okawa Y., Kaimoto S., Uchihashi M., Fukai K., et al.: Inhibition of p53 preserves Parkin-mediated mitophagy and pancreatic β-cell function in diabetes. Proc. Natl. Acad. Sci. U. S. A. Feb. 111, 3116–3121 (2014)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, School of Medicine, Pole Recherche 1, place de Verdun, 59045, Lille Cedex, France

    Remi Neviere

  2. LIRIC INSERM U995/Team “Glycation: from inflammation to aging”, Lille University, Villeneuve d’Ascq, France

    Remi Neviere, Yichi Yu, Lei Wang, Frederic Tessier & Eric Boulanger

  3. School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Yichi Yu & Lei Wang

Authors
  1. Remi Neviere
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yichi Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frederic Tessier
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric Boulanger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Remi Neviere.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Neviere, R., Yu, Y., Wang, L. et al. Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions. Glycoconj J 33, 607–617 (2016). https://doi.org/10.1007/s10719-016-9679-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-016-9679-x

Keywords

Search

Navigation