Top

18-12-2023 | Chronic Kidney Disease | Review Article

ROS-Activated TRPM2 Channel: Calcium Homeostasis in Cardiovascular/renal System and Speculation in Cardiorenal Syndrome

Authors: Zihan Chen, Zaihua Cheng, Congcong Ding, Tianyu Cao, Ling Chen, Hong Wang, Junpei Li, Xiao Huang

Published in: Cardiovascular Drugs and Therapy

Abstract

The transient receptor potential melastatin 2 (TRPM2) channel is a nonselective calcium channel that is sensitive to oxidative stress (OS), and is widely expressed in multiple organs, such as the heart, kidney, and brain, which is inextricably related to calcium dyshomeostasis and downstream pathological events. Due to the increasing global burden of kidney or cardiovascular diseases (CVDs), safe and efficient drugs specific to novel targets are imperatively needed. Notably, investigation of the possibility to regard the TRPM2 channel as a new therapeutic target in ROS-related CVDs or renal diseases is urgently required because the roles of the TRPM2 channel in heart or kidney diseases have not received enough attention and thus have not been fully elaborated. Therefore, we aimed to review the involvement of the TRPM2 channel in cardiovascular disorders related to kidney or typical renal diseases and attempted to speculate about TRPM2-mediated mechanisms of cardiorenal syndrome (CRS) to provide representative perspectives for future research about novel and effective therapeutic strategies.

Hecquet CM, Ahmmed GU, Vogel SM, Malik AB. Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circ Res. 2008;102(3):347–55. https://doi.org/10.1161/CIRCRESAHA.107.160176.CrossRefPubMed

Miller BA, Zhang W. TRP channels as mediators of oxidative stress. Adv Exp Med Biol. 2011;704:531–44. https://doi.org/10.1007/978-94-007-0265-3_29.CrossRefPubMed

Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4(7):517–29. https://doi.org/10.1038/nrm1155.CrossRefPubMed

Antonenkov VD, Grunau S, Ohlmeier S, Hiltunen JK. Peroxisomes are oxidative organelles. Antioxid Redox Signal. 2010;13(4):525–37. https://doi.org/10.1089/ars.2009.2996.CrossRefPubMed

Sun-Wada G-H, Wada Y, Futai M. Lysosome and lysosome-related organelles responsible for specialized functions in higher organisms, with special emphasis on vacuolar-type proton ATPase. Cell Struct Funct. 2003;28(5):455–63. https://doi.org/10.1247/csf.28.455.CrossRefPubMed

Nohl H, Gille L. The bifunctional activity of ubiquinone in lysosomal membranes. Biogerontology. 2002;3(1–2):125–31. https://doi.org/10.1023/a:1015288220217.CrossRefPubMed

Groenendyk J, Michalak M. Endoplasmic reticulum quality control and apoptosis. Acta Biochim Pol. 2005;52(2):381–95. https://doi.org/10.18388/abp.2005_3451.CrossRefPubMed

Cribb AE, Peyrou M, Muruganandan S, Schneider L. The endoplasmic reticulum in xenobiotic toxicity. Drug Metab Rev. 2005;37(3):405–42. https://doi.org/10.1080/03602530500205135.CrossRefPubMed

Brieger K, Schiavone S, Miller FJ, Krause KH. Reactive oxygen species: from health to disease. Swiss Med Wkly. 2012;142:w13659. https://doi.org/10.4414/smw.2012.13659.CrossRefPubMed

10.

Ali SS, Ahsan H, Zia MK, Siddiqui T, Khan FH. Understanding oxidants and antioxidants: Classical team with new players. J Food Biochem. 2020;44(3):e13145. https://doi.org/10.1111/jfbc.13145.CrossRefPubMed

11.

Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363–83. https://doi.org/10.1038/s41580-020-0230-3.CrossRefPubMed

12.

Jagannathan R, Patel SA, Ali MK, Narayan KMV. Global Updates on Cardiovascular Disease Mortality Trends and Attribution of Traditional Risk Factors. Curr Diab Rep. 2019;19(7):44. https://doi.org/10.1007/s11892-019-1161-2.CrossRefPubMed

13.

Collaboration GCKD. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709–33. https://doi.org/10.1016/S0140-6736(20)30045-3.CrossRef

14.

Ostapchenko VG, Chen M, Guzman MS, et al. The transient receptor potential melastatin 2 (TRPM2) channel contributes to β-amyloid oligomer-related neurotoxicity and memory impairment. J Neurosci. 2015;35(45):15157–69. https://doi.org/10.1523/JNEUROSCI.4081-14.2015.CrossRefPubMedPubMedCentral

15.

Gelderblom M, Melzer N, Schattling B, et al. Transient receptor potential melastatin subfamily member 2 cation channel regulates detrimental immune cell invasion in ischemic stroke. Stroke. 2014;45(11):3395–402. https://doi.org/10.1161/STROKEAHA.114.005836.CrossRefPubMed

16.

Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis. 2013;3(4):461–91. https://doi.org/10.3233/JPD-130230.CrossRefPubMedPubMedCentral

17.

Miller BA. TRPM2 in Cancer. Cell Calcium. 2019;80. https://doi.org/10.1016/j.ceca.2019.03.002.

18.

Cosens DJ, Manning A. Abnormal electroretinogram from a Drosophila mutant. Nature. 1969;224(5216):285–7. https://doi.org/10.1038/224285a0.CrossRefPubMed

19.

Yue Z, Xie J, Yu AS, et al. Role of TRP channels in the cardiovascular system. Am J Physiol Heart Circ Physiol. 2015;308(3):H157-HH82. https://doi.org/10.1152/ajpheart.00457.2014.CrossRefPubMed

20.

Vázquez E, Valverde MA. A review of TRP channels splicing. Semin Cell Dev Biol. 2006;17(6):607–17. https://doi.org/10.1016/j.semcdb.2006.11.004.CrossRefPubMed

21.

Venkatachalam K, Montell C. TRP channels. Annu Rev Biochem. 2007;76:387–417. https://doi.org/10.1146/annurev.biochem.75.103004.142819.CrossRefPubMedPubMedCentral

22.

Uemura T, Kudoh J, Noda S, Kanba S, Shimizu N. Characterization of human and mouse TRPM2 genes: identification of a novel N-terminal truncated protein specifically expressed in human striatum. Biochem Biophys Res Commun. 2005;328(4):1232–43. https://doi.org/10.1016/j.bbrc.2005.01.086.CrossRefPubMed

23.

Fonfria E, Murdock PR, Cusdin FS, et al. Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res. 2006;26(3):159–78. https://doi.org/10.1080/10799890600637506.

24.

Wang L, Fu TM, Zhou Y, et al. Structures and gating mechanism of human TRPM2. Science. 2018;362(6421). https://doi.org/10.1126/science.aav4809.

25.

Huang Y, Winkler PA, Sun W, Lü W, Du J. Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature. 2018;562(7725):145–9. https://doi.org/10.1038/s41586-018-0558-4.CrossRefPubMed

26.

Hara Y, Wakamori M, Ishii M, et al. LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell. 2002;9(1):163–73. https://doi.org/10.1016/s1097-2765(01)00438-5.CrossRefPubMed

27.

Nazıroğlu M. TRPM2 cation channels, oxidative stress and neurological diseases: where are we now? Neurochem Res. 2011;36(3):355–66. https://doi.org/10.1007/s11064-010-0347-4.CrossRefPubMed

28.

Perraud AL, Fleig A, Dunn CA, et al. ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature. 2001;411(6837):595–9. https://doi.org/10.1038/35079100.CrossRefPubMed

29.

Syed Mortadza SA, Wang L, Li D, Jiang L-H. TRPM2 channel-mediated ROS-sensitive Ca(2+) signaling mechanisms in immune cells. Front Immunol. 2015;6:407. https://doi.org/10.3389/fimmu.2015.00407.CrossRefPubMedPubMedCentral

30.

Wang G, Cao L, Liu X, et al. Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation. Dev Cell. 2016;38(5):453–62. https://doi.org/10.1016/j.devcel.2016.07.014.CrossRefPubMedPubMedCentral

31.

Du J, Xie J, Yue L. Modulation of TRPM2 by acidic pH and the underlying mechanisms for pH sensitivity. J Gen Physiol. 2009;134(6):471–88. https://doi.org/10.1085/jgp.200910254.CrossRefPubMedPubMedCentral

32.

Kühn FJP, Heiner I, Lückhoff A. TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose. Pflugers Arch. 2005;451(1):212–9. https://doi.org/10.1007/s00424-005-1446-y.CrossRefPubMed

33.

Fonfria E, Marshall ICB, Benham CD, et al. TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol. 2004;143(1):186–92. https://doi.org/10.1038/sj.bjp.0705914.CrossRefPubMedPubMedCentral

34.

Buelow B, Song Y, Scharenberg AM. The Poly(ADP-ribose) polymerase PARP-1 is required for oxidative stress-induced TRPM2 activation in lymphocytes. J Biol Chem. 2008;283(36):24571–83. https://doi.org/10.1074/jbc.M802673200.CrossRefPubMedPubMedCentral

35.

Wang L, Fu T-M, Zhou Y, et al. Structures and gating mechanism of human TRPM2. Science. 2018;362:6421. https://doi.org/10.1126/science.aav4809.CrossRef

36.

Huang Y, Roth B, Lü W, Du J. Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel. Elife. 2019;8. https://doi.org/10.7554/eLife.50175.

37.

Cahill PA, Redmond EM. Vascular endothelium - Gatekeeper of vessel health. Atherosclerosis. 2016;248. https://doi.org/10.1016/j.atherosclerosis.2016.03.007.

38.

Sun L, Yau H-Y, Wong W-Y, et al. Role of TRPM2 in H(2)O(2)-induced cell apoptosis in endothelial cells. PLoS One. 2012;7(8):e43186. https://doi.org/10.1371/journal.pone.0043186.CrossRefPubMedPubMedCentral

39.

Abuarab N, Munsey TS, Jiang L-H, Li J, Sivaprasadarao A. High glucose-induced ROS activates TRPM2 to trigger lysosomal membrane permeabilization and Zn2+-mediated mitochondrial fission. Sci Signal. 2017;10(490). https://doi.org/10.1126/scisignal.aal4161.

40.

Hecquet CM, Zhang M, Mittal M, et al. Cooperative interaction of trp melastatin channel transient receptor potential (TRPM2) with its splice variant TRPM2 short variant is essential for endothelial cell apoptosis. Circ Res. 2014;114(3):469–79. https://doi.org/10.1161/CIRCRESAHA.114.302414.CrossRefPubMed

41.

Wang T, Wang L, Moreno-Vinasco L, et al. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation. Part Fibre Toxicol. 2012;9:35. https://doi.org/10.1186/1743-8977-9-35.CrossRefPubMedPubMedCentral

42.

Mittal M, Nepal S, Tsukasaki Y, et al. Neutrophil activation of endothelial cell-expressed TRPM2 mediates transendothelial neutrophil migration and vascular injury. Circ Res. 2017;121(9):1081–91. https://doi.org/10.1161/CIRCRESAHA.117.311747.CrossRefPubMedPubMedCentral

43.

Newby AC, Zaltsman AB. Fibrous cap formation or destruction–the critical importance of vascular smooth muscle cell proliferation, migration and matrix formation. Cardiovasc Res. 1999;41(2):345–60. https://doi.org/10.1016/S0008-6363(98)00286-7.CrossRefPubMed

44.

Ru X, Zheng C, Zhao Q, et al. Transient receptor potential channel M2 contributes to neointimal hyperplasia in vascular walls. Biochim Biophys Acta. 2015;1852(7):1360–71. https://doi.org/10.1016/j.bbadis.2015.03.014.CrossRefPubMed

45.

Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science. 2000;290(5497):1717–21. https://doi.org/10.1126/science.290.5497.1717.CrossRefPubMedPubMedCentral

46.

Tai S, Hu X-Q, Peng D-Q, Zhou S-H, Zheng X-L. The roles of autophagy in vascular smooth muscle cells. Int J Cardiol. 2016;211:1–6. https://doi.org/10.1016/j.ijcard.2016.02.128.CrossRefPubMed

47.

Zhao Q, Li J, Ko W-H, et al. TRPM2 promotes autophagic degradation in vascular smooth muscle cells. Sci Rep. 2020;10(1):20719. https://doi.org/10.1038/s41598-020-77620-y.CrossRefPubMedPubMedCentral

48.

Chistiakov DA, Melnichenko AA, Myasoedova VA, Grechko AV, Orekhov AN. Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl). 2017;95(11):1153–65. https://doi.org/10.1007/s00109-017-1575-8.CrossRefPubMed

49.

Zong P, Feng J, Yue Z, et al. TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages. Nat Cardiovasc Res. 2022;1(4):344–60. https://doi.org/10.1038/s44161-022-00027-7.CrossRefPubMedPubMedCentral

50.

Senoner T, Dichtl W. Oxidative stress in cardiovascular diseases: still a therapeutic target? Nutrients. 2019;11(9). https://doi.org/10.3390/nu11092090.

51.

Zholos A, Johnson C, Burdyga T, Melanaphy D. TRPM channels in the vasculature. Adv Exp Med Biol. 2011;704:707–29. https://doi.org/10.1007/978-94-007-0265-3_37.CrossRefPubMed

52.

Ozcan L, Cristina de Souza J, Harari AA, et al. Activation of calcium/calmodulin-dependent protein kinase II in obesity mediates suppression of hepatic insulin signaling. Cell Metab. 2013;18(6):803–15. https://doi.org/10.1016/j.cmet.2013.10.011.CrossRefPubMed

53.

Sun L, Liu Y-L, Ye F, et al. Free fatty acid-induced H2O2 activates TRPM2 to aggravate endothelial insulin resistance via Ca2+-dependent PERK/ATF4/TRB3 cascade in obese mice. Free Rad Biol Med. 2019;143:288–99. https://doi.org/10.1016/j.freeradbiomed.2019.08.018.CrossRefPubMed

54.

Gao M, Du Y, Xie J-W, et al. Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca2+-dependent CaMKII/JNK cascade. Metabolism. 2018;85:313–24. https://doi.org/10.1016/j.metabol.2018.05.005.CrossRefPubMed

55.

Alves-Lopes R, Neves KB, Anagnostopoulou A, et al. Crosstalk between vascular redox and calcium signaling in hypertension involves TRPM2 (transient receptor potential melastatin 2) cation channel. Hypertension. 2020;75(1):139–49. https://doi.org/10.1161/HYPERTENSIONAHA.119.13861.CrossRefPubMed

56.

Rabinovich-Nikitin I, Lieberman B, Martino TA, Kirshenbaum LA. Circadian-regulated cell death in cardiovascular diseases. Circulation. 2019;139(7):965–80. https://doi.org/10.1161/CIRCULATIONAHA.118.036550.CrossRefPubMed

57.

Zhang Z, Zhang W, Jung DY, et al. TRPM2 Ca2+ channel regulates energy balance and glucose metabolism. Am J Physiol Endocrinol Metab. 2012;302(7):E807-EE16. https://doi.org/10.1152/ajpendo.00239.2011.CrossRefPubMedPubMedCentral

58.

Yang KT, Chang WL, Yang PC, et al. Activation of the transient receptor potential M2 channel and poly(ADP-ribose) polymerase is involved in oxidative stress-induced cardiomyocyte death. Cell Death Differ. 2006;13(10):1815–26. https://doi.org/10.1038/sj.cdd.4401813.CrossRefPubMed

59.

Takahashi N, Kozai D, Kobayashi R, Ebert M, Mori Y. Roles of TRPM2 in oxidative stress. Cell Calcium. 2011;50(3):279–87. https://doi.org/10.1016/j.ceca.2011.04.006.CrossRefPubMed

60.

Hiroi T, Wajima T, Negoro T, et al. Neutrophil TRPM2 channels are implicated in the exacerbation of myocardial ischaemia/reperfusion injury. Cardiovasc Res. 2013;97(2):271–81. https://doi.org/10.1093/cvr/cvs332.CrossRefPubMed

61.

Markó L, Mannaa M, Haschler TN, Krämer S, Gollasch M. Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2. Acta Physiol (Oxf). 2017;219(3):589–612. https://doi.org/10.1111/apha.12828.CrossRefPubMed

62.

Yamamoto S, Shimizu S, Kiyonaka S, et al. TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration. Nat Med. 2008;14(7):738–47. https://doi.org/10.1038/nm1758.CrossRefPubMedPubMedCentral

63.

Fonfria E, Marshall ICB, Boyfield I, et al. Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J Neurochem. 2005;95(3):715–23. https://doi.org/10.1111/j.1471-4159.2005.03396.x.CrossRefPubMed

64.

Miller BA. The role of TRP channels in oxidative stress-induced cell death. J Membr Biol. 2006;209(1):31–41. https://doi.org/10.1007/s00232-005-0839-3.CrossRefPubMed

65.

Du J, Xie J, Yue L. Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proc Natl Acad Sci USA. 2009;106(17):7239–44. https://doi.org/10.1073/pnas.0811725106.CrossRefPubMedPubMedCentral

66.

Inserte J, Hernando V, Garcia-Dorado D. Contribution of calpains to myocardial ischaemia/reperfusion injury. Cardiovasc Res. 2012;96(1):23–31. https://doi.org/10.1093/cvr/cvs232.CrossRefPubMed

67.

De Rosa S, Antonelli M, Ronco C. Hypothermia and kidney: a focus on ischaemia-reperfusion injury. Nephrol Dial Transplant. 2017;32(2):241–7. https://doi.org/10.1093/ndt/gfw038.CrossRefPubMed

68.

Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl. 2004;91:S56–61. https://doi.org/10.1111/j.1523-1755.2004.09109.x.CrossRef

69.

Furuichi K, Wada T, Kaneko S, Murphy PM. Roles of chemokines in renal ischemia/reperfusion injury. Front Biosci. 2008;13:4021–8. https://doi.org/10.2741/2990.CrossRefPubMed

70.

Stroo I, Stokman G, Teske GJD, et al. Chemokine expression in renal ischemia/reperfusion injury is most profound during the reparative phase. Int Immunol. 2010;22(6):433–42. https://doi.org/10.1093/intimm/dxq025.CrossRefPubMedPubMedCentral

71.

Kher A, Meldrum KK, Wang M, et al. Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury. Cardiovasc Res. 2005;67(4):594–603. https://doi.org/10.1016/j.cardiores.2005.05.005.CrossRefPubMed

72.

Robledo-Avila FH, Ruiz-Rosado JD, Brockman KL, Partida-Sánchez S. The TRPM2 ion channel regulates inflammatory functions of neutrophils during Listeria monocytogenes infection. Front Immunol. 2020;11:97. https://doi.org/10.3389/fimmu.2020.00097.CrossRefPubMedPubMedCentral

73.

Dizin E, Hasler U, Nlandu-Khodo S, et al. Albuminuria induces a proinflammatory and profibrotic response in cortical collecting ducts via the 24p3 receptor. Am J Physiol Renal Physiol. 2013;305(7):F1053-F1F63. https://doi.org/10.1152/ajprenal.00006.2013.CrossRefPubMed

74.

Nazıroğlu M, Çiğ B, Yazğan Y, et al. Albumin evokes Ca2+-induced cell oxidative stress and apoptosis through TRPM2 channel in renal collecting duct cells reduced by curcumin. Sci Rep. 2019;9(1):12403. https://doi.org/10.1038/s41598-019-48716-x.CrossRefPubMedPubMedCentral

75.

Cai Y, Chen J, Liu J, et al. Identification of six hub genes and two key pathways in two rat renal fibrosis models based on bioinformatics and RNA-seq transcriptome analyses. Front Mol Biosci. 2022;9:1035772. https://doi.org/10.3389/fmolb.2022.1035772.CrossRefPubMedPubMedCentral

76.

Wang Y, Chen L, Wang K, et al. Suppression of TRPM2 reduces renal fibrosis and inflammation through blocking TGF-β1-regulated JNK activation. Biomed Pharmacother. 2019;120:109556. https://doi.org/10.1016/j.biopha.2019.109556.CrossRefPubMed

77.

Klahr S, Morrissey J. Progression of chronic renal disease. Am J Kidney Dis. 2003;41(3 Suppl 1):S3–7. https://doi.org/10.1053/ajkd.2003.50074.CrossRefPubMed

78.

Yildar M, Aksit H, Korkut O, et al. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res. 2014;187(2):683–9 10.1016/j.jss.2013.11.009.CrossRefPubMed

79.

Nagase M, Fujita T. Role of Rac1-mineralocorticoid-receptor signalling in renal and cardiac disease. Nat Rev Nephrol. 2013;9(2):86–98. https://doi.org/10.1038/nrneph.2012.282.CrossRefPubMed

80.

Gao G, Wang W, Tadagavadi RK, et al. TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1. J Clin Invest. 2014;124(11):4989–5001. https://doi.org/10.1172/JCI76042.CrossRefPubMedPubMedCentral

81.

Schriewer JM, Peek CB, Bass J, Schumacker PT. ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion. J Am Heart Assoc. 2013;2(2):e000159. https://doi.org/10.1161/JAHA.113.000159.CrossRefPubMedPubMedCentral

82.

Zhang F, Xie R, Munoz FM, Lau SS, Monks TJ. PARP-1 hyperactivation and reciprocal elevations in intracellular Ca2+ during ROS-induced nonapoptotic cell death. Toxicol Sci. 2014;140(1):118–34. https://doi.org/10.1093/toxsci/kfu073.CrossRefPubMedPubMedCentral

83.

Giorgi C, Baldassari F, Bononi A, et al. Mitochondrial Ca(2+) and apoptosis. Cell Calcium. 2012;52(1):36–43. https://doi.org/10.1016/j.ceca.2012.02.008.CrossRefPubMedPubMedCentral

84.

Çakır M, Tekin S, Taşlıdere A, et al. Protective effect of N-(p-amylcinnamoyl) anthranilic acid, phospholipase A2 enzyme inhibitor, and transient receptor potential melastatin-2 channel blocker against renal ischemia-reperfusion injury. J Cell Biochem. 2019;120(3):3822–32. https://doi.org/10.1002/jcb.27664.CrossRefPubMed

85.

Armağan HH, Nazıroğlu M. Glutathione depletion induces oxidative injury and apoptosis via TRPM2 channel activation in renal collecting duct cells. Chem Biol Interact. 2021;334:109306. https://doi.org/10.1016/j.cbi.2020.109306.CrossRefPubMed

86.

Kurata Y, Tanaka T, Cernecka H, Eitner F, Nangaku M. TRPM2 Plays a Minor Role in AKI and Kidney Fibrosis. Kidney360. 2022;3(1):153–7. https://doi.org/10.34067/KID.0005492021.CrossRefPubMed

87.

LaFavers KA, Macedo E, Garimella PS, et al. Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel. Sci Transl Med. 2019;11(512). https://doi.org/10.1126/scitranslmed.aaw3639.

88.

Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Circulation. 2023. https://doi.org/10.1161/CIR.0000000000001184.

89.

Jentzer JC, van Diepen S, Barsness GW, et al. Changes in comorbidities, diagnoses, therapies and outcomes in a contemporary cardiac intensive care unit population. Am Heart J. 2019;215:12–9. https://doi.org/10.1016/j.ahj.2019.05.012.CrossRefPubMed

90.

Sinha SS, Sjoding MW, Sukul D, et al. Changes in primary noncardiac diagnosesover time among elderly cardiac intensive care unit patients in the United States. Circ Cardiovasc Qual Outcomes. 2017;10(8):e003616. https://doi.org/10.1161/CIRCOUTCOMES.117.003616.CrossRefPubMedPubMedCentral

91.

Holland EM, Moss TJ. Acute noncardiovascular illness in the cardiac intensive care unit. J Am Coll Cardiol. 2017;69(16):1999–2007. https://doi.org/10.1016/j.jacc.2017.02.033.CrossRefPubMed

92.

Krumholz HM, Chen YT, Vaccarino V, et al. Correlates and impact on outcomes of worsening renal function in patients > or =65 years of age with heart failure. Am J Cardiol. 2000;85(9):1110–3. https://doi.org/10.1016/s0002-9149(00)00705-0.CrossRefPubMed

93.

Murgier M, Bertoletti L, Darmon M, et al. Frequency and prognostic impact of acute kidney injury in patients with acute pulmonary embolism. Data from the RIETE registry. Int J Cardiol. 2019;291:121–6. https://doi.org/10.1016/j.ijcard.2019.04.083.CrossRefPubMed

94.

Anand IS. Cardiorenal syndrome: a cardiologist’s perspective of pathophysiology. Clin J Am Soc Nephrol. 2013;8(10):1800–7. https://doi.org/10.2215/CJN.04090413.CrossRefPubMedPubMedCentral

95.

Damman K, van Deursen VM, Navis G, et al. Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J Am Coll Cardiol. 2009;53(7):582–8. https://doi.org/10.1016/j.jacc.2008.08.080.CrossRefPubMed

96.

Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B. The severe cardiorenal syndrome: “Guyton revisited.” Eur Heart J. 2005;26(1):11–7. https://doi.org/10.1093/eurheartj/ehi020.CrossRefPubMed

97.

Singh K, Xiao L, Remondino A, Sawyer DB, Colucci WS. Adrenergic regulation of cardiac myocyte apoptosis. J Cell Physiol. 2001;189(3):257–65. https://doi.org/10.1002/jcp.10024.CrossRefPubMed

98.

Jackson G, Gibbs CR, Davies MK, Lip GY. ABC of heart failure. Pathophysiology. BMJ. 2000;320(7228):167–70. https://doi.org/10.1136/bmj.320.7228.167.CrossRefPubMedPubMedCentral

99.

Li L, Lee EW, Ji H, Zukowska Z. Neuropeptide Y-induced acceleration of postangioplasty occlusion of rat carotid artery. Arterioscler Thromb Vasc Biol. 2003;23(7):1204–10. https://doi.org/10.1161/01.ATV.0000071349.30914.25.CrossRefPubMed

100.

Kajstura J, Cigola E, Malhotra A, et al. Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol. 1997;29(3):859–70. https://doi.org/10.1006/jmcc.1996.0333.CrossRefPubMed

101.

House AA, Anand I, Bellomo R, et al. Definition and classification of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference. Nephrol Dial Transplant. 2010;25(5):1416–20. https://doi.org/10.1093/ndt/gfq136.CrossRefPubMed

102.

Hatamizadeh P, Fonarow GC, Budoff MJ, et al. Cardiorenal syndrome: pathophysiology and potential targets for clinical management. Nat Rev Nephrol. 2013;9(2). https://doi.org/10.1038/nrneph.2012.279.

103.

Messerli FH, Rimoldi SF, Bangalore S. The transition from hypertension to heart failure: contemporary update. JACC Heart Fail. 2017;5(8):543–51. https://doi.org/10.1016/j.jchf.2017.04.012.CrossRefPubMed

104.

Ishizu T, Seo Y, Kameda Y, et al. Left ventricular strain and transmural distribution of structural remodeling in hypertensive heart disease. Hypertension. 2014;63(3):500–6. https://doi.org/10.1161/HYPERTENSIONAHA.113.02149.CrossRefPubMed

105.

Valero-Muñoz M, Backman W, Sam F. Murine models of heart failure with preserved ejection fraction: a “fishing expedition.” JACC Basic Transl Sci. 2017;2(6):770–89. https://doi.org/10.1016/j.jacbts.2017.07.013.CrossRefPubMedPubMedCentral

106.

Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146–603. https://doi.org/10.1161/CIR.0000000000000485.CrossRefPubMedPubMedCentral

107.

Leader CJ, Wilkins GT, Walker RJ. The effect of spironolactone on cardiac and renal fibrosis following myocardial infarction in established hypertension in the transgenic Cyp1a1Ren2 rat. PLoS One. 2021;16(11):e0260554. https://doi.org/10.1371/journal.pone.0260554.CrossRefPubMedPubMedCentral

108.

Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Circulation. 2003;108(17):2154–69. https://doi.org/10.1161/01.HYP.0000102971.85504.7c.CrossRefPubMed

109.

Ruiz-Ortega M, Ruperez M, Lorenzo O, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int Suppl. 2002;82:S12–22. https://doi.org/10.1046/j.1523-1755.62.s82.4.x.CrossRef

110.

Sedeek M, Nasrallah R, Touyz RM, Hébert RL. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe. J Am Soc Nephrol. 2013;24(10):1512–8. https://doi.org/10.1681/ASN.2012111112.CrossRefPubMedPubMedCentral

111.

Bauersachs J, Bouloumié A, Fraccarollo D, et al. Endothelial dysfunction in chronic myocardial infarction despite increased vascular endothelial nitric oxide synthase and soluble guanylate cyclase expression: role of enhanced vascular superoxide production. Circulation. 1999;100(3):292–8. https://doi.org/10.1161/01.cir.100.3.292.CrossRefPubMed

112.

Hallström S, Franz M, Gasser H, et al. S-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia. Cardiovasc Res. 2008;77(3):506–14. https://doi.org/10.1093/cvr/cvm052.CrossRefPubMed

113.

Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest. 1994;94(4):1621–8. https://doi.org/10.1172/JCI117504.CrossRefPubMedPubMedCentral

114.

Gottlieb RA, Gruol DL, Zhu JY, Engler RL. Preconditioning rabbit cardiomyocytes: role of pH, vacuolar proton ATPase, and apoptosis. J Clin Invest. 1996;97(10):2391–8. https://doi.org/10.1172/JCI118683.CrossRefPubMedPubMedCentral

115.

Condorelli G, Roncarati R, Ross J, et al. Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function. Proc Natl Acad Sci USA. 2001;98(17):9977–82. https://doi.org/10.1073/pnas.161120198.CrossRefPubMedPubMedCentral

116.

Yamamoto S, Yang G, Zablocki D, et al. Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy. J Clin Invest. 2003;111(10):1463–74. https://doi.org/10.1172/JCI17459.CrossRefPubMedPubMedCentral

117.

Nadal-Ginard B, Kajstura J, Anversa P, Leri A. A matter of life and death: cardiac myocyte apoptosis and regeneration. J Clin Invest. 2003;111(10):1457–9. https://doi.org/10.1172/JCI18611.CrossRefPubMedPubMedCentral

118.

Rosenkranz S, Howard LS, Gomberg-Maitland M, Hoeper MM. Systemic consequences of pulmonary hypertension and right-sided heart failure. Circulation. 2020;141(8):678–93. https://doi.org/10.1161/CIRCULATIONAHA.116.022362.CrossRefPubMed

119.

Hemmi S, Matsumoto N, Jike T, et al. Proximal tubule morphology in rats with renal congestion: a study involving the in vivo cryotechnique. Med Mol Morphol. 2015;48(2). https://doi.org/10.1007/s00795-014-0084-x.

120.

Bitker L, Sens F, Payet C, et al. Presence of kidney disease as an outcome predictor in patients with pulmonary arterial hypertension. Am J Nephrol. 2018;47(2):134–43. https://doi.org/10.1159/000487198.CrossRefPubMed

121.

Park S, Lee S, Kim Y, et al. Atrial fibrillation and kidney function: a bidirectional Mendelian randomization study. Eur Heart J. 2021;42(29):2816–23. https://doi.org/10.1093/eurheartj/ehab291.CrossRefPubMed

122.

Düzen IV, Yavuz F, Vuruskan E, et al. Leukocyte TRP channel gene expressions in patients with non-valvular atrial fibrillation. Sci Rep. 2017;7(1):9272. https://doi.org/10.1038/s41598-017-10039-0.CrossRefPubMedPubMedCentral

123.

Carney EF. Thrombosis: new mechanism of thrombus formation in CKD. Nat Rev Nephrol. 2016;12(12):715. https://doi.org/10.1038/nrneph.2016.155.CrossRefPubMed

124.

Saxena PR. Interaction between the renin-angiotensin-aldosterone and sympathetic nervous systems. J Cardiovasc Pharmacol. 1992;19(Suppl 6):S80-SS8. https://doi.org/10.1097/00005344-199219006-00013.CrossRefPubMed

125.

Wanner C, Amann K, Shoji T. The heart and vascular system in dialysis. Lancet. 2016;388(10041):276–84. https://doi.org/10.1016/S0140-6736(16)30508-6.CrossRefPubMed

126.

Mitsnefes MM, Daniels SR, Schwartz SM, et al. Severe left ventricular hypertrophy in pediatric dialysis: prevalence and predictors. Pediatr Nephrol. 2000;14(10–11):898–902. https://doi.org/10.1007/s004670000303.CrossRefPubMed

127.

Kramann R, Erpenbeck J, Schneider RK, et al. Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD. J Am Soc Nephrol. 2014;25(10):2351–65. https://doi.org/10.1681/ASN.2013070734.CrossRefPubMedPubMedCentral

128.

Methven S, Steenkamp R, Fraser S. UK Renal Registry 19th Annual Report: chapter 5 survival and causes of death in UK adult patients on renal replacement therapy in 2015: national and centre-specific analyses. Nephron. 2017;137(Suppl 1):117–50. https://doi.org/10.1159/000481367.CrossRefPubMed

129.

Matsushita K, van der Velde M, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–81. https://doi.org/10.1016/S0140-6736(10)60674-5.CrossRefPubMedPubMedCentral

130.

Gregg LP, Adams-Huet B, Li X, et al. Effect modification of chronic kidney disease on the association of circulating and imaging cardiac biomarkers with outcomes. J Am Heart Assoc. 2017;6(7). https://doi.org/10.1161/JAHA.116.005235.

131.

Georgianos PI, Sarafidis PA, Liakopoulos V. Arterial stiffness: a novel risk factor for kidney injury progression? Am J Hypertens. 2015;28(8):958–65. https://doi.org/10.1093/ajh/hpv004.CrossRefPubMed

132.

Liu S, Lekawanvijit S, Kompa AR, et al. Cardiorenal syndrome: pathophysiology, preclinical models, management and potential role of uraemic toxins. Clin Exp Pharmacol Physiol. 2012;39(8):692–700. https://doi.org/10.1111/j.1440-1681.2011.05632.x.CrossRefPubMed

133.

Rockey DC, Bell PD, Hill JA. Fibrosis--a common pathway to organ injury and failure. N Engl J Med. 2015;372(12):1138–49. https://doi.org/10.1056/NEJMra1300575.CrossRefPubMed

134.

Song J, Navarro-Garcia JA, Wu J, et al. Chronic kidney disease promotes atrial fibrillation via inflammasome pathway activation. J Clin Invest. 2023;133(19). https://doi.org/10.1172/JCI167517.

135.

Qiu H, Ji C, Wu H, Zou C. Chronic kidney disease-induced atrial structural remodeling and atrial fibrillation: more studies on the pathological mechanism are encouraged. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(7):671–3. https://doi.org/10.1007/s00210-018-1494-4.CrossRefPubMed

136.

Verheule S, Sato T, Everett T, et al. Increased vulnerability to atrial fibrillation in transgenic mice with selective atrial fibrosis caused by overexpression of TGF-beta1. Circ Res. 2004;94(11):1458–65.CrossRefPubMedPubMedCentral

137.

Nakajima H, Nakajima HO, Salcher O, et al. Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1) transgene in the heart. Circ Res. 2000;86(5):571–9.CrossRefPubMed

138.

Shimizu T, Macey TA, Quillinan N, et al. Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury. J Cereb Blood Flow Metab. 2013;33(10):1549–55. https://doi.org/10.1038/jcbfm.2013.105.CrossRefPubMedPubMedCentral

139.

Guinamard R, Simard C, Del Negro C. Flufenamic acid as an ion channel modulator. Pharmacol Ther. 2013;138(2):272–84. https://doi.org/10.1016/j.pharmthera.2013.01.012.CrossRefPubMedPubMedCentral

140.

Chen G-L, Zeng B, Eastmond S, et al. Pharmacological comparison of novel synthetic fenamate analogues with econazole and 2-APB on the inhibition of TRPM2 channels. Br J Pharmacol. 2012;167(6):1232–43. https://doi.org/10.1111/j.1476-5381.2012.02058.x.CrossRefPubMedPubMedCentral

141.

Hill K, McNulty S, Randall AD. Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole. Naunyn Schmiedebergs Arch Pharmacol. 2004;370(4):227–37. https://doi.org/10.1007/s00210-004-0981-y.CrossRefPubMed

142.

Kraft R, Grimm C, Frenzel H, Harteneck C. Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid. Br J Pharmacol. 2006;148(3):264–73. https://doi.org/10.1038/sj.bjp.0706739.CrossRefPubMedPubMedCentral

143.

Togashi K, Inada H, Tominaga M. Inhibition of the transient receptor potential cation channel TRPM2 by 2-aminoethoxydiphenyl borate (2-APB). Br J Pharmacol. 2008;153(6):1324–30. https://doi.org/10.1038/sj.bjp.0707675.CrossRefPubMedPubMedCentral

144.

Eraslan E, Tanyeli A, Polat E, Polat E. 8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury. J Cell Physiol. 2019;234(4):4572–81. https://doi.org/10.1002/jcp.27236.CrossRefPubMed

145.

Fourgeaud L, Dvorak C, Faouzi M, et al. Pharmacology of JNJ-28583113: A novel TRPM2 antagonist. Eur J Pharmacol. 2019;853:299–307. https://doi.org/10.1016/j.ejphar.2019.03.043.CrossRefPubMed

146.

Alemán OR, Mora N, Rosales C. The antibody receptor Fc gamma receptor IIIb induces calcium entry via transient receptor potential melastatin 2 in human neutrophils. Front Immunol. 2021;12:657393. https://doi.org/10.3389/fimmu.2021.657393.CrossRefPubMedPubMedCentral

147.

Yu P, Liu Z, Yu X, et al. Direct gating of the TRPM2 channel by cADPR via specific interactions with the ADPR binding pocket. Cell Rep. 2019:27(12). https://doi.org/10.1016/j.celrep.2019.05.067.

148.

Yu X, Xie Y, Zhang X, et al. Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel. Cell Rep. 2021;37(7):110025. https://doi.org/10.1016/j.celrep.2021.110025.CrossRefPubMed

149.

Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128. https://doi.org/10.1016/S0140-6736(12)61728-0.CrossRefPubMed

150.

Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation. 2001;104(23):2855–64. https://doi.org/10.1161/hc4701.099488.CrossRefPubMed

151.

Eckardt K-U, Coresh J, Devuyst O, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet. 2013;382(9887):158–69. https://doi.org/10.1016/S0140-6736(13)60439-0.CrossRefPubMed

152.

Morine KJ, Paruchuri V, Qiao X, et al. Endoglin selectively modulates transient receptor potential channel expression in left and right heart failure. Cardiovasc Pathol. 2016;25(6):478–82. https://doi.org/10.1016/j.carpath.2016.08.004.CrossRefPubMedPubMedCentral

153.

Morgan SJ, Elangbam CS, Berens S, et al. Use of animal models of human disease for nonclinical safety assessment of novel pharmaceuticals. Toxicol Pathol. 2013;41(3):508–18. https://doi.org/10.1177/0192623312457273.CrossRefPubMed

Title: ROS-Activated TRPM2 Channel: Calcium Homeostasis in Cardiovascular/renal System and Speculation in Cardiorenal Syndrome
Authors: Zihan Chen
Zaihua Cheng
Congcong Ding
Tianyu Cao
Ling Chen
Hong Wang
Junpei Li
Xiao Huang
Publication date: 18-12-2023
Publisher: Springer US
Keyword: Chronic Kidney Disease
Published in: Cardiovascular Drugs and Therapy
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI: https://doi.org/10.1007/s10557-023-07531-3

2024 ESC Congress

Noise pollution dangerous for heart health

02-09-2024 Myocardial Infarction News

Two studies underscore the adverse impact of noise pollution on the risk for and prognosis after myocardial infarction.

Post-TAVI follow up: deploying virtual assistants

02-09-2024 Transcatheter Aortic Valve Implantation News

Antihypertensives: more effective at morning or night?

02-09-2024 Hypertension News

Low Lp(a) levels unlikely to increase the risk of diabetes

02-09-2024 Type 2 Diabetes News

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

Electrocardiography Training Course

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date.

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

Keynote webinar | Spotlight on medication adherence

Webinar | 27-06-2024 | 18:00 (CEST)

Medication non-adherence is a major barrier to effective healthcare delivery; half of all patients do not follow their doctor’s recommendations or treatment plan.

Our experts explain the fundamentals with a practical discussion of how to manage non-adherence in two common scenarios: hypertension and asthma control.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Watch now

2024 ESC Congress

Springer Medicine

Abstract

Please log in to get access to this content

2024 ESC Congress

Noise pollution dangerous for heart health

Post-TAVI follow up: deploying virtual assistants

Antihypertensives: more effective at morning or night?

Low Lp(a) levels unlikely to increase the risk of diabetes

» View more highlights on the 2024 ESC Congress hub page

A quick guide to ECGs

Keynote webinar | Spotlight on medication adherence