RAGE Modulates Hypoxia/Reoxygenation Injury in Adult Murine Cardiomyocytes via JNK and GSK-3β Signaling Pathways
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BACKGROUND: Advanced glycation end-products (AGEs) have been implicated in diverse pathological settings including diabetes, inflammation and acute ischemia/reperfusion injury in the heart. AGEs interact with the receptor for AGEs (RAGE) and transduce signals through activation of MAPKs and proapoptotic pathways. In the current study, adult cardiomyocytes were studied in an in vitro ischemia/reperfusion (I/R) injury model to delineate the molecular mechanisms underlying RAGE-mediated injury due to hypoxia/reoxygenation (H/R). METHODOLOGY/PRINCIPAL FINDINGS: Cardiomyocytes isolated from adult wild-type (WT), homozygous RAGE-null (RKO), and WT mice treated with soluble RAGE (sRAGE) were subjected to hypoxia for 30 minutes alone or followed by reoxygenation for 1 hour. In specific experiments, RAGE ligand carboxymethyllysine (CML)-AGE (termed "CML" in this manuscript) was evaluated in vitro. LDH, a marker of cellular injury, was assayed in the supernatant in the presence or absence of signaling inhibitor-treated cardiomyocytes. Cardiomyocyte levels of heterogeneous AGEs were measured using ELISA. A pronounced increase in RAGE expression along with AGEs was observed in H/R vs. normoxia in WT cardiomyocytes. WT cardiomyocytes after H/R displayed increased LDH release compared to RKO or sRAGE-treated cardiomyocytes. Our results revealed significant increases in phospho-JNK in WT cardiomyocytes after H/R. In contrast, neither RKO nor sRAGE-treated cardiomyocytes exhibited increased phosphorylation of JNK after H/R stress. The impact of RAGE deletion on GSK-3beta phosphorylation in the cardiomyocytes subjected to H/R revealed significantly higher levels of phospho-GSK-3beta/total GSK-3beta in RKO, as well as in sRAGE-treated cardiomyocytes versus WT cardiomyocytes after H/R. Further investigation established a key role for Akt, which functions upstream of GSK-3beta, in modulating H/R injury in adult cardiomyocytes. CONCLUSIONS/SIGNIFICANCE: These data illustrate key roles for RAGE-ligand interaction in the pathogenesis of cardiomyocyte injury induced by hypoxia/reoxygenation and indicate that the effects of RAGE are mediated by JNK activation and dephosphorylation of GSK-3beta. The outcome in this study lends further support to the potential use of RAGE blockade as an adjunctive therapy for protection of the ischemic heart.
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Activation of RAGE by its ligands upregulates inflammatory signalling pathways including NF-κB, phosphoinositide 3-kinase, JAK-STAT and MAPK, leading to induction of pro-inflammatory cytokines such as TNF.
“Activation of RAGe by its ligands results in the upregulation of several inflammatory signalling pathways, including, but not limited to, NF-κb, phospho inositide 3-kinase, Janus kinase (JAK)–signal transducer and activator of transcription (STAT) and MAPK signalling pathways, which lead to induction of pro-inflammatory cytokines such as TNF19,91,95,96.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [91]
RAGE is a transmembrane receptor expressed by immune cells, endothelial cells, cardiomyocytes and neurons.
“RAGe is a transmembrane receptor that is expressed by immune cells, endothelial cells, cardiomyocytes and neurons89–91.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [91]
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GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084 · see citing works
Park, L., Raman, K. G., Lee, K. J., Lu, Y., Ferran, L. J., Chow, W. S., Stern, D. M., & Schmidt, A. M. (1998) · Nature Medicine · doi:10.1038/2012 · Cited by 1,103 · see citing works
Self-citationKajstura, J., Cheng, W. N., Krzysztof Reiss, F., CLARK, W. A., Sonnenblick, E. H., Krajewski, S., Reed, J., Olivetti, G., & Anversa, P. (1996) · PubMed · Cited by 1,039 · see citing works
Juhaszova, M., Zorov, D. B., Kim, S.-H., Pepe, S., Fu, Q., Fishbein, K. W., Ziman, B. D., Wang, S., Kirsti Ytrehus, B., Antos, C. L., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19906 · Cited by 1,029 · see citing works
Coghlan, M. P., Culbert, A. A., Cross, D. A. E., Corcoran, S. L., Yates, J. W., Pearce, N. J., Rausch, O., Murphy, G. J., Carter, P. S., Cox, L. R., et al. (2000) · Chemistry & Biology · doi:10.1016/s1074-5521(00)00025-9 · Cited by 901 · see citing works
Fujio, Y., Nguyen, T. U., Wencker, D., Kitsis, R. N., & Walsh, K. (2000) · Circulation · doi:10.1161/01.cir.101.6.660 · Cited by 846 · see citing works
Survey of Studies Examining Mammalian Cardiomyocyte DNA Synthesis
Soonpaa, M. H., & Field, L. J. (1998) · Circulation Research · doi:10.1161/01.res.83.1.15 · Cited by 558 · see citing works
CREB DNA binding activity is inhibited by glycogen synthase kinase‐3β and facilitated by lithium
Grimes, C. A., & Jope, R. S. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00495.x · Cited by 437 · see citing works
Ventricular Myocytes Are Not Terminally Differentiated in the Adult Mammalian Heart
Anversa, P., & Kajstura, J. (1998) · Circulation Research · doi:10.1161/01.res.83.1.1 · Cited by 389 · see citing works
Peptide and Protein Library Screening Defines Optimal Substrate Motifs for AKT/PKB
Obata, T., Yaffe, M. B., Leparc, G., Piro, E. T., Maegawa, H., Kashiwagi, A., Kikkawa, R., & Cantley, L. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m005497200 · Cited by 388 · see citing works
Tong, H., Imahashi, K., Steenbergen, C., & Murphy, E. (2002) · Circulation Research · doi:10.1161/01.res.0000012567.95445.55 · Cited by 377 · see citing works
Glycogen Synthase Kinase-3: a Putative Molecular Target for Lithium Mimetic Drugs
Gould, T. D., & Manji, H. K. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300731 · Cited by 377 · see citing works
Central role of RAGE-dependent neointimal expansion in arterial restenosis
Sakaguchi, T., Yan, S. F., Yan, S. D., Belov, D., Rong, L., Sousa, M. M., Andrassy, M., Marso, S. P., Duda, S., Arnold, B., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17115 · Cited by 370 · see citing works
Self-citationMacLellan, W. R., & Schneider, M. D. (1997) · Circulation Research · doi:10.1161/01.res.81.2.137 · Cited by 361 · see citing works
Das, A., Xi, L., & Kukreja, R. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m404706200 · Cited by 334 · see citing works
Aoki, H., Kang, P. M., Hampe, J., Yoshimura, K., Noma, T., Matsuzaki, M., & Izumo, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m112355200 · Cited by 332 · see citing works
Central role of RAGE-dependent neointimal expansion in arterial restenosis
Sakaguchi, T., Yan, S. F., Yan, S. D., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317115 · Cited by 313 · see citing works
Self-citationGlycogen Synthase Kinase-3 - An Overview of An Over-Achieving Protein Kinase
Kockeritz, L. K., Doble, B. W., Patel, S., & Woodgett, J. R. (2006) · Current Drug Targets · doi:10.2174/1389450110607011377 · Cited by 285 · see citing works
Judging a Protein by More Than Its Name: GSK-3
Woodgett, J. R. (2001) · Science s STKE · doi:10.1126/stke.2001.100.re12 · Cited by 279 · see citing works
Receptor for Advanced-Glycation End Products: Key Modulator of Myocardial Ischemic Injury
Bucciarelli, L. G., Kaneko, M., Ananthakrishnan, R., Harja, E., Lee, L. K., Hwang, Y. C., Lerner, S., Bakr, S., Li, Q., Lu, Y., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.575993 · Cited by 256 · see citing works
Self-citationActivation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress
Dougherty, C. J., Kubasiak, L. A., Prentice, H. M., Andreka, P. G., Bishopric, N. H., & Webster, K. A. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3620561 · Cited by 159 · see citing works
Aleshin, A., Ananthakrishnan, R., Li, Q., Rosario, R., Lu, Y., Qu, W., Song, F., Bakr, S., Szabolcs, M., D'Agati, V., et al. (2008) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01210.2007 · Cited by 143 · see citing works
Self-citationRAGE limits regeneration after massive liver injury by coordinated suppression of TNF-α and NF-κB
Cataldegirmen, G., Zeng, S., Feirt, N. M., Ippagunta, N., Dun, H., Qu, W., Lu, Y., Rong, L., Hofmann, M. A., Kislinger, T., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20040934 · Cited by 137 · see citing works
Self-citationRong, L., Yan, S., Wendt, T., Hans, D., Pachydaki, S. I., Bucciarelli, L. G., Adebayo, A., Qu, W., Lu, Y., Kostov, K., et al. (2004) · The FASEB Journal · doi:10.1096/fj.04-1900com · Cited by 136 · see citing works
Self-citationMEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes
Minamino, T., Yujiri, T., Papst, P. J., Chan, E. D., Johnson, G. L., & Terada, N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15127 · Cited by 135 · see citing works
Shao, Z., Bhattacharya, K., Hsich, E., Park, L., Walters, B. M., Germann, U. A., Wang, Y., Kyriakis, J. M., Mohanlal, R. W., Kuida, K., et al. (2005) · Circulation Research · doi:10.1161/01.res.0000197781.20524.b9 · Cited by 125 · see citing works
Kaiser, R. A., Liang, Q., Bueno, O. F., Huang, Y., Lackey, T., Klevitsky, R., Hewett, T. E., & Molkentin, J. D. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500684200 · Cited by 121 · see citing works
Hreniuk, D., Garay, M., Gaarde, W. A., Monia, B. P., McKay, R. A., & Cioffi, C. L. (2001) · Molecular Pharmacology · doi:10.1124/mol.59.4.867 · Cited by 119 · see citing works
Cytoprotection by Jun Kinase During Nitric Oxide–Induced Cardiac Myocyte Apoptosis
Andreka, P. G., Zang, J., Dougherty, C. J., Slepak, T. I., Webster, K. A., & Bishopric, N. H. (2001) · Circulation Research · doi:10.1161/01.res.88.3.305 · Cited by 119 · see citing works
RAGE and Modulation of Ischemic Injury in the Diabetic Myocardium
Bucciarelli, L. G., Ananthakrishnan, R., Hwang, Y. C., Kaneko, M., Song, F., Sell, D. R., Strauch, C., Monnier, V. M., Yan, S. F., Schmidt, A. M., et al. (2008) · Diabetes · doi:10.2337/db07-0326 · Cited by 113 · see citing works
Self-citationActivation of the JNK pathway is important for cardiomyocyte death in response to simulated ischemia
He, H., Li, H.-L., Lin, A., & Gottlieb, R. A. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400572 · Cited by 97 · see citing works
Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress
Dougherty, C. J., Kubasiak, L. A., Prentice, H. M., et al. (2002) · Biochemical Journal · doi:10.1042/bj3620561 · Cited by 94 · see citing works
Dougherty, C. J., Kubasiak, L. A., Frazier, D. P., Li, H., Xiong, W., Bishopric, N. H., & Webster, K. A. (2004) · The FASEB Journal · doi:10.1096/fj.04-1505com · Cited by 92 · see citing works
Cicconi, S., Ventura, N., Pastore, D., Bonini, P., Nardo, P. D., Lauro, R., & Marlier, L. N. (2003) · Journal of Cellular Physiology · doi:10.1002/jcp.10219 · Cited by 70 · see citing works
Markou, T., Cullingford, T. E., Giraldo, A., Weiss, S. C., Alsafi, A., Fuller, S. J., Clerk, A., & Sugden, P. H. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.10.004 · Cited by 66 · see citing works
Kumar, Y., & Tatu, U. S. (2003) · PROTEOMICS · doi:10.1002/pmic.200390065 · Cited by 56 · see citing works
Yun, H., Kim, H.-S., Lee, S., Kang, I., Kim, S. S., Choe, W., & Ha, J. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn259 · Cited by 39 · see citing works
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Sterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
Receptor for AGE (RAGE): Signaling mechanisms in the pathogenesis of diabetes and its complications
Ramasamy, R., Yan, S. F., & Schmidt, A. M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06320.x · Cited by 521 · see citing works
Self-citationCellular signalling of the receptor for advanced glycation end products (RAGE)
Xie, J., Méndez, J. D., Méndez-Valenzuela, V., & Aguilar-Hernández, M. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.013 · Cited by 515 · see citing works
Fishman, S. L., Sonmez, H., Basman, C., Singh, V., & Poretsky, L. (2018) · Molecular Medicine · doi:10.1186/s10020-018-0060-3 · Cited by 330 · see citing works
Murakami, K., Murata, N., Noda, Y., Tahara, S., Kaneko, T., Kinoshita, N., Hatsuta, H., Murayama, S., Barnham, K. J., Irie, K., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.279208 · Cited by 241 · see citing works
RAGE in tissue homeostasis, repair and regeneration
Sorci, G., Riuzzi, F., Giambanco, I., & Donato, R. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.10.021 · Cited by 229 · see citing works
Egaña-Gorroño, L., López‐Díez, R., Yepuri, G., Ramirez, L. S., Reverdatto, S., Gugger, P. F., Shekhtman, A. G., Ramasamy, R., & Schmidt, A. M. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00037 · Cited by 210 · see citing works
Self-citationWang, J., Hsieh, C., Wang, M., Wang, X., Wu, Z., Jiang, D., Liao, B., Zhang, X., Yang, B., He, Q., et al. (2021) · Nature Machine Intelligence · doi:10.1038/s42256-021-00403-1 · Cited by 193 · see citing works
Glycation exacerbates the neuronal toxicity of β-amyloid
Li, X.-H., Du, L.-L., Cheng, X.-S., Jiang, X., Zhang, Y., Lv, B.-L., Liu, R., Wang, J.-Z., & Zhou, X.-W. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.180 · Cited by 178 · see citing works
Aldini, G., Vistoli, G., Štefek, M., Chondrogianni, N., Grune, T., Sereikaitė, J., Sadowska‐Bartosz, I., & Bartosz, G. (2013) · Free Radical Research · doi:10.3109/10715762.2013.792926 · Cited by 151 · see citing works
Ramasamy, R., Yan, S. F., & Schmidt, A. M. (2012) · Vascular Pharmacology · doi:10.1016/j.vph.2012.06.004 · Cited by 151 · see citing works
Self-citationc-Jun N-Terminal Kinases (JNKs) in Myocardial and Cerebral Ischemia/Reperfusion Injury
Shvedova, M., Anfinogenova, Y., Atochina‐Vasserman, E. N., Schepetkin, I. A., & Atochin, D. N. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00715 · Cited by 131 · see citing works
Small Molecule Inhibition of Ligand-Stimulated RAGE-DIAPH1 Signal Transduction
Manigrasso, M. B., Pan, J., Rai, V., Zhang, J., Reverdatto, S., Quadri, N., DeVita, R. J., Ramasamy, R., Shekhtman, A. G., & Schmidt, A. M. (2016) · Scientific Reports · doi:10.1038/srep22450 · Cited by 121 · see citing works
Self-citationMitra, A., Basak, T., Datta, K., Naskar, S., Sengupta, S., & Sarkar, S. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.114 · Cited by 120 · see citing works
Lysophosphatidic acid targets vascular and oncogenic pathways via RAGE signaling
Rai, V., Touré, F., Chitayat, S., Pei, R., Song, F., Li, Q., Zhang, J., Rosario, R., Ramasamy, R., Chazin, W., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120873 · Cited by 117 · see citing works
Self-citationThe multiple faces of RAGE – opportunities for therapeutic intervention in aging and chronic disease
Ramasamy, R., Shekhtman, A. G., & Schmidt, A. M. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1111873 · Cited by 110 · see citing works
Self-citationRAGE Expression in Human T Cells: A Link between Environmental Factors and Adaptive Immune Responses
Akirav, E. M., Preston‐Hurlburt, P., Garyu, J., Henegariu, O., Clynes, R., Schmidt, A. M., & Herold, K. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034698 · Cited by 102 · see citing works
Self-citationRAGE: a new frontier in chronic airways disease
Sukkar, M. B., Ullah, M. A., Gan, W. J., Wark, P. A. B., Chung, K. F., Hughes, J. M., Armour, C. L., & Phipps, S. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01984.x · Cited by 98 · see citing works
Mao, Y., Cai, W., Sun, X., Dai, P., Li, X., Wang, Q., Huang, X., He, B., Wang, P. P., Wu, G., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0718-3 · Cited by 94 · see citing works
Ramasamy, R., & Schmidt, A. M. (2012) · Current Heart Failure Reports · doi:10.1007/s11897-012-0089-5 · Cited by 79 · see citing works
Self-citationMacLean, M., Derk, J., Ruiz, H. H., Juranek, J. K., Ramasamy, R., & Schmidt, A. M. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.03.012 · Cited by 69 · see citing works
Self-citationThe anti-inflamm-aging and hepatoprotective effects of huperzine A in d-galactose-treated rats
Ruan, Q., Liu, F., Gao, Z., Kong, D., Hu, X., Shi, D., Bao, Z., & Yu, Z. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2012.12.005 · Cited by 65 · see citing works
Hypoxia driven glycation: Mechanisms and therapeutic opportunities
Khan, M. I., Rath, S., Adhami, V. M., & Mukhtar, H. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.05.008 · Cited by 64 · see citing works
Velotta, J. B., Kimura, N., Chang, S. H., Chung, J., Itoh, S., Rothbard, J. B., Yang, P. C., Steinman, L., Robbins, R. C., & Fischbein, M. P. (2011) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2011.02.072 · Cited by 59 · see citing works
Lin, L., Zhong, K., Sun, Z., Wu, G., & Ding, G. (2011) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-011-1067-0 · Cited by 57 · see citing works
Zhu, Z., Zhu, J., Zhao, X., Yang, K., Lu, L., Zhang, F., Shen, W., & Zhang, R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133414 · Cited by 53 · see citing works
Self-citationTian, Y., Pan, D., Chordia, M. D., French, B. A., Kron, I. L., & Yang, Z. (2016) · Basic Research in Cardiology · doi:10.1007/s00395-016-0583-0 · Cited by 52 · see citing works
Jiang, X., Guo, C., Zeng, X., Li, H., Chen, B., & Du, F. (2015) · APOPTOSIS · doi:10.1007/s10495-015-1130-4 · Cited by 51 · see citing works
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Oliveira, J., Soares, A. A. S. M., & Sposito, A. C. (2018) · Advances in clinical chemistry · doi:10.1016/bs.acc.2017.12.002 · Cited by 50 · see citing works
Hong, J.-E., Ku, S. H., Lee, M. S., Jeong, J. H., Mok, H., Choi, D., & Kim, S. H. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.05.025 · Cited by 48 · see citing works
Nevière, R., Yu, Y.-C., Wang, L., Tessier, F. J., & Boulanger, É. (2016) · Glycoconjugate Journal · doi:10.1007/s10719-016-9679-x · Cited by 46 · see citing works
Cardiomyocyte culture — an update on the in vitro cardiovascular model and future challenges
Parameswaran, S., Kumar, S., Verma, R. S., & Sharma, R. K. (2013) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2013-0161 · Cited by 45 · see citing works
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O’Shea, K. M., Ananthakrishnan, R., Li, Q., Quadri, N., Thiagarajan, D., Sreejit, G., Wang, L., Zirpoli, H., Aranda, J. F., Alberts, A. S., et al. (2017) · EBioMedicine · doi:10.1016/j.ebiom.2017.11.012 · Cited by 45 · see citing works
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Jensen, L. J. N., Flyvbjerg, A., & Bjerre, M. (2015) · BioMed Research International · doi:10.1155/2015/815942 · Cited by 44 · see citing works
Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice
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Self-citationBillah, M., Ridiandries, A., Allahwala, U. K., Mudaliar, H., Dona, A. C., Hunyor, S. N., Khachigian, L. M., & Bhindi, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051692 · Cited by 40 · see citing works
Liu, Y., Qu, Y., Wang, R., Ma, Y., Xia, C., Gao, C., Liu, J., Lian, K., Aibing, X., Lu, X., et al. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00075.2012 · Cited by 40 · see citing works
Detrimental effects of acute hyperglycaemia on the rat heart
Mapanga, R. F., Joseph, D. E., Symington, B., Garson, K. L., Kimar, C. P., Kelly-Laubscher, R. F., & Essop, M. F. (2013) · Acta Physiologica · doi:10.1111/apha.12184 · Cited by 38 · see citing works
Oh, J., Lee, J., Piao, C., Jeong, J. H., & Lee, M. (2019) · Biomaterials Science · doi:10.1039/c8bm01621f · Cited by 37 · see citing works
Billah, M., Ridiandries, A., Rayner, B. S., Allahwala, U. K., Dona, A. C., Khachigian, L. M., & Bhindi, R. (2019) · Basic Research in Cardiology · doi:10.1007/s00395-019-0763-9 · Cited by 36 · see citing works
Yang, J., Zhang, F., Shi, H., Gao, Y., Dong, Z., Ma, L., Sun, X., Li, X., Chang, S., Wang, Z., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900115rr · Cited by 34 · see citing works
Role of DJ‐1 in Modulating Glycative Stress in Heart Failure
Shimizu, Y., Nicholson, C. K., Polavarapu, R., Pantner, Y., Husain, A., Naqvi, N., Chin, L., Li, L., & Calvert, J. W. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.014691 · Cited by 34 · see citing works
Lu, Y., Zhao, Y., Xu, S., Ding, F., Jin, C., Fu, G., & Weng, S. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14022242 · Cited by 32 · see citing works
Wang, J., Wang, X., Sun, H., Wang, M., Zeng, Y., Jiang, D., Wu, Z., Liu, Z., Liao, B., Yao, X., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01179 · Cited by 32 · see citing works
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Batkulwar, K., Bansode, S. B., Patil, G. V., Godbole, R. K., Kazi, R. S., Chinnathambi, S., Shanmugam, D., & Kulkarni, M. J. (2014) · PROTEOMICS · doi:10.1002/pmic.201400169 · Cited by 30 · see citing works
Roy, D., Ramasamy, R., & Schmidt, A. M. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315527 · Cited by 29 · see citing works
Self-citationLiu, Y., Yu, M., Zhang, Z., Yu, Y., Chen, Q., Zhang, W., & Zhao, X. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.07.008 · Cited by 29 · see citing works
Beeraka, N. M., Bovilla, V. R., Doreswamy, S. H., Puttalingaiah, S., Srinivasan, A., & Madhunapantula, S. V. (2021) · Cancers · doi:10.3390/cancers13020281 · Cited by 28 · see citing works
Receptor for advanced glycation end‐products: Biological significance and imaging applications
Dobrucki, I. T., Miskalis, A., Nelappana, M. B., Applegate, C. C., Woźniak, M., Czerwiński, A. A., Kalinowski, L., & Dobrucki, L. W. (2023) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1935 · Cited by 27 · see citing works
Pyridoxamine improves survival and limits cardiac dysfunction after MI
Deluyker, D., Ferferieva, V., Driesen, R. B., Verboven, M., Lambrichts, I., & Bito, V. (2017) · Scientific Reports · doi:10.1038/s41598-017-16255-y · Cited by 27 · see citing works
Guo, C., Zeng, X., Song, J., Zhang, M., Wang, H., Xu, X., Du, F., & Chen, B. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911923 · Cited by 26 · see citing works
Sala, M. A., Chen, C., Zhang, Q., Do-Umehara, H. C., Wu, W., Misharin, A. V., Waypa, G. B., Fang, D., Budinger, G. R. S., Liu, S., et al. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000440 · Cited by 26 · see citing works
PEG-modified nano liposomes co-deliver Apigenin and RAGE-siRNA to protect myocardial ischemia injury
Liu, C., Zhang, X., Yang, H., Zhao, M., Liu, Y., Zhao, R., Li, Z., & Sun, M. J. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123673 · Cited by 25 · see citing works
Guo, C., Jiang, X., Zeng, X., Wang, H., Li, H., Du, F., & Chen, B. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.011 · Cited by 25 · see citing works
Dang, M., Zeng, X., Chen, B., Wang, H., Li, H., Liu, Y., Zhang, X., Cao, X., Du, F., & Guo, C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.437 · Cited by 24 · see citing works
Bangar, N. S., Gvalani, A., Ahmad, S., Khan, M. S., & Tupe, R. S. (2022) · Glycobiology · doi:10.1093/glycob/cwac060 · Cited by 22 · see citing works
Uremic Toxin–Targeting as a Therapeutic Strategy for Preventing Cardiorenal Syndrome
Taguchi, K., Elias, B. C., Brooks, C. R., Ueda, S., & Fukami, K. (2019) · Circulation Journal · doi:10.1253/circj.cj-19-0872 · Cited by 22 · see citing works
Mota, K. O., de Vasconcelos, C. M. L., Kirshenbaum, L. A., & Dhalla, N. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157311 · Cited by 21 · see citing works
Ruhs, S., Naß, N., Bartling, B., Brömme, H., Leuner, B., Somoza, V., Friess, U., Silber, R., & Simm, A. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.001 · Cited by 21 · see citing works
Tekabe, Y., Luma, J., Qing, L., Schmidt, A. M., Ramasamy, R., & Johnson, L. L. (2012) · JACC. Cardiovascular imaging · doi:10.1016/j.jcmg.2011.09.016 · Cited by 20 · see citing works
Self-citationDiabetes impairs periosteal progenitor regenerative potential
Doherty, L., Wan, M., Kalajzić, I., & Sanjay, A. (2020) · Bone · doi:10.1016/j.bone.2020.115764 · Cited by 19 · see citing works
DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart
Pantner, Y., Polavarapu, R., Chin, L., Li, L., Shimizu, Y., & Calvert, J. W. (2021) · Scientific Reports · doi:10.1038/s41598-021-98722-1 · Cited by 19 · see citing works
Abdillahi, M., Ananthakrishnan, R., Vedantham, S., Shang, L., Zhu, Z., Rosario, R., Zirpoli, H., Bohren, K. M., Gabbay, K. H., & Ramasamy, R. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00999.2011 · Cited by 19 · see citing works
Self-citationRogala, S., Ali, T., Melissari, M., Währisch, S., Schuster, P., Sarre, A., Emídio, R. C., Boettger, T., Rogg, E.-M., Kaur, J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42760-y · Cited by 17 · see citing works
Goury, A., Meghraoui, A., Belmokhtar, K., Vuiblet, V., Ortillon, J., Jaisson, S., Devy, J., Naour, R. L., Tabary, T., Cohen, J. H. M., et al. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402342 · Cited by 17 · see citing works
Self-citationSamidurai, A., Ockaili, R. A., Cain, C. K., Roh, S. K., Filippone, S. M., Kraskauskas, D., Kukreja, R. C., & Das, A. (2020) · iScience · doi:10.1016/j.isci.2020.101863 · Cited by 17 · see citing works
Son, M., Kang, W. C., Oh, S., Bayarsaikhan, D., Ahn, H., Lee, J., Park, H., Lee, S., Choi, J., Lee, H. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11773-1 · Cited by 17 · see citing works
Dang, M., Zeng, X., Chen, B., Wang, H., Li, H., Du, F., & Guo, C. (2018) · Laboratory Investigation · doi:10.1038/s41374-018-0102-z · Cited by 16 · see citing works
The Role of Ranolazine in Heart Failure-Current Concepts
Kourampi, I., Katsioupa, M., Oikonomou, E. K., Tsigkou, V., Marinos, G., Goliopoulou, A., Κατσαρού, Ο., Kalogeras, K. I., Theofilis, P., Tsatsaragkou, A., et al. (2023) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2023.09.066 · Cited by 15 · see citing works
Xiong, J., Zhao, W., Lin, Y., Yao, L., Huang, G., Yu, C., Dong, H., Xiao, G., Zhao, H., & Cai, S. (2018) · International Immunopharmacology · doi:10.1016/j.intimp.2018.03.037 · Cited by 14 · see citing works
Effects of protein glycation and protective mechanisms against glycative stress
Najjar, J. A., & Calvert, J. W. (2024) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2024.102464 · Cited by 13 · see citing works
Zhang, J., Ding, W., Liu, J., Wan, J., & Wang, M. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.122.027862 · Cited by 12 · see citing works
Xia, Z., Zhao, B., Gao, W.-W., Liu, Y., Jiang, M., Liu, L., Yuan, Q., & Hou, J. (2017) · Neural Regeneration Research · doi:10.4103/1673-5374.217337 · Cited by 12 · see citing works
Zhang, H., Lin, A., Zhai, C., Lai, T., Gong, X., Wang, M., Wu, H., Ye, T., Wang, L., & Tawulie, D. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157694 · Cited by 10 · see citing works
Molecular Generation with Reduced Labeling through Constraint Architecture
Wang, J., Zeng, Y., Sun, H., Wang, J., Wang, X., Jin, R., Wang, M., Zhang, X., Cao, D., Chen, X., et al. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00579 · Cited by 10 · see citing works
The role of sRAGE in cardiovascular diseases
Delrue, C., Delanghe, J., & Speeckaert, M. M. (2023) · Advances in clinical chemistry · doi:10.1016/bs.acc.2023.08.005 · Cited by 10 · see citing works
Mechanistic underpinnings of AGEs-RAGE via DIAPH1 in ischemic, diabetic, and failing hearts
Yepuri, G., Hasan, S. N., Kumar, V. S., Manigrasso, M. B., Theophall, G. G., Shekhtman, A. G., Schmidt, A. M., & Ramasamy, R. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00685.2024 · Cited by 9 · see citing works
Self-citationNeuroprotective Effect of Huperzine A on d -Galactose-Induced Hearing Dysfunction
Li, C., & Shi, S. (2019) · Ear Nose & Throat Journal · doi:10.1177/0145561319864570 · Cited by 9 · see citing works
Rong, J., Ye, S., Liang, M., Chen, G., Liu, H., Zhang, J., & Wu, Z. (2013) · ASAIO Journal · doi:10.1097/mat.0b013e318290504e · Cited by 9 · see citing works
Bayarsaikhan, D., Bayarsaikhan, G., Lee, J., & Lee, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415630 · Cited by 8 · see citing works
Advanced Glycation End Products and Diabetes
Hadzi‐Petrushev, N., Angelovski, M., & Mladenov, M. I. (2023) · Contemporary Endocrinology · doi:10.1007/978-3-031-39721-9_5 · Cited by 6 · see citing works
Gupta, A., Hadj‐Moussa, H., Al-attar, R., Seibel, B. A., & Storey, K. B. (2021) · Physiological and Biochemical Zoology · doi:10.1086/714097 · Cited by 3 · see citing works
Hegab, Z. (2012) · Research Explorer (The University of Manchester)
Abdillahi, M. (2012) · doi:10.7916/d8959qhc
Self-citationRole of Tumour Necrosis Factor Alpha (TNFa) in ischaemic and pharmacological postconditioning
Lacerda, L. (2010) · Open University of Cape Town (University of Cape Town)
Blackburn, N. J. (2017) · uO Research (University of Ottawa) · doi:10.20381/ruor-20651
Touré, F., Cohen, J. H. M., Schmidt, A., Rieu, P., Devy, J., Tabary, T., Ortillon, J., & Meghraoui, A. (2015)
Self-citationResearch Progress on the Receptor of Advanced Glycation End Products in Cardiovascular Diseases
何, 端. (2025) · Advances in Clinical Medicine · doi:10.12677/acm.2025.151217
Receptor for Advanced Glycation End Products in Cardiovascular and Diabetic Complication(s)
Rani, R., Malik, P., & Mukherjee, T. K. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815322521125010010
Teissier, T. (2019) · theses.fr (ABES) · doi:10.70675/f49bc069z5ee6z4c49zb46fz0a1413dbba95
Role of the RAGE signaling pathway in myocardial ischemia/reperfusion injury
Sun, P., Zhang, C., & Shi, Z. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118538
- Authors
- Shang, L., Ananthakrishnan, R., Li, Q., Quadri, N., Abdillahi, M., Zhu, Z., Qu, W., Rosario, R., Touré, F., Yan, S. F., Schmidt, A. M., & Ramasamy, R.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Ramasamy, Ravichandran
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-04-09
- Volume
- 5
- Issue
- 4
- Pages
- e10092
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2852407
- OpenAlex
- W1965286369
- Cited by
- 93
- References
- 35
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 2 · 2013: 9 · 2012: 13
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging (P01AG026467, AG026467)
- National Heart, Lung, and Blood Institute (P01HL060901, HL 61783, HL60901, R01HL061783)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- receptor for advanced glycation end products, advanced glycation end products, hypoxia/reoxygenation injury, cardiomyocytes, JNK signaling, GSK3β signaling, Akt, carboxymethyllysine, ischemia-reperfusion injury, soluble RAGE, cardiac injury, MAPK signaling, apoptosis, myocardial ischemia-reperfusion injury
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Hypoxia, Ligands, Receptors, Immunologic, Signal Transduction, Reperfusion Injury, Glycation End Products, Advanced, Myocytes, Cardiac, Glycogen Synthase Kinase 3, JNK Mitogen-Activated Protein Kinases, Mice
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