Skip to content
2000
Volume 21, Issue 2
  • ISSN: 1573-403X
  • E-ISSN: 1875-6557

Abstract

Diabetic Cardiomyopathy (DCM) is a notable consequence of diabetes mellitus, distinguished by cardiac dysfunction that occurs separately from coronary artery disease or hypertension. A recent study has revealed an intricate interaction of pathogenic processes that contribute to DCM. Important aspects involve the dysregulation of glucose metabolism, resulting in heightened oxidative stress and impaired mitochondrial function. In addition, persistent high blood sugar levels stimulate inflammatory pathways, which contribute to the development of heart fibrosis and remodelling. Additionally, changes in the way calcium is managed and the presence of insulin resistance are crucial factors in the formation and advancement of DCM. This may be due to the involvement of many molecular mechanistic pathways such as NLRP3, NF-κB, PKC, and MAPK with their downstream associated signaling pathways. Gaining a comprehensive understanding of these newly identified pathogenic pathways is crucial in order to design precise therapy approaches that can enhance the results for individuals suffering from diabetes. In addition, this review offers an in-depth review of not just pathogenic pathways and molecular mechanistic pathways but also diagnostic methods, treatment options, and clinical trials.

Loading

Article metrics loading...

/content/journals/ccr/10.2174/011573403X331870241025094307
2024-11-04
2025-05-11
Loading full text...

Full text loading...

References

  1. Martín-TimónI. Sevillano-CollantesC. Segura-GalindoA. Del Cañizo-GómezF.J. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?World J. Diabetes20145444447010.4239/wjd.v5.i4.444 25126392
    [Google Scholar]
  2. ZhouY. SuoW. ZhangX. Targeting epigenetics in diabetic cardiomyopathy: Therapeutic potential of flavonoids.Biomed. Pharmacother.202315711402510.1016/j.biopha.2022.114025 36399824
    [Google Scholar]
  3. TangZ. WangP. DongC. ZhangJ. WangX. PeiH. Oxidative stress signaling mediated pathogenesis of diabetic cardiomyopathy.Oxid. Med. Cell. Longev.202220221810.1155/2022/5913374 35103095
    [Google Scholar]
  4. DeviS. ChauhanS. MannanA. SinghT.G. Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective.Inflammopharmacology2024321307317 38085446
    [Google Scholar]
  5. KimA.H. JangJ.E. HanJ. Current status on the therapeutic strategies for heart failure and diabetic cardiomyopathy.Biomed. Pharmacother.202214511246310.1016/j.biopha.2021.112463 34839258
    [Google Scholar]
  6. BehlT. BungauS. KumarK. Pleotropic Effects of polyphenols in cardiovascular system.Biomed. Pharmacother.202013011071410.1016/j.biopha.2020.110714 34321158
    [Google Scholar]
  7. YangL. ZhaoD. RenJ. YangJ. Endoplasmic reticulum stress and protein quality control in diabetic cardiomyopathy.Biochim. Biophys. Acta Mol. Basis Dis.20151852220921810.1016/j.bbadis.2014.05.006 24846717
    [Google Scholar]
  8. LeeY.B. HanK. KimB. Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study.Cardiovasc. Diabetol.201918115710.1186/s12933‑019‑0953‑7 31733656
    [Google Scholar]
  9. Grubić RotkvićP. PlaninićZ. Liberati PršoA.M. ŠikićJ. GalićE. RotkvićL. The mystery of diabetic cardiomyopathy: From early concepts and underlying mechanisms to novel therapeutic possibilities.Int. J. Mol. Sci.20212211597310.3390/ijms22115973 34205870
    [Google Scholar]
  10. Corb AronR.A. AbidA. VesaC.M. Recognizing the benefits of pre-/probiotics in metabolic syndrome and type 2 diabetes mellitus considering the influence of Akkermansia muciniphila as a key gut bacterium.Microorganisms20219361810.3390/microorganisms9030618 33802777
    [Google Scholar]
  11. TrachanasK. SiderisS. AggeliC. Diabetic cardiomyopathy: from pathophysiology to treatment.Hellenic J. Cardiol.2014555411421 25243440
    [Google Scholar]
  12. RublerS. DlugashJ. YuceogluY.Z. KumralT. BranwoodA.W. GrishmanA. New type of cardiomyopathy associated with diabetic glomerulosclerosis.Am. J. Cardiol.197230659560210.1016/0002‑9149(72)90595‑4 4263660
    [Google Scholar]
  13. SearsB. PerryM. The role of fatty acids in insulin resistance.Lipids Health Dis.201514112110.1186/s12944‑015‑0123‑1 26415887
    [Google Scholar]
  14. GoldbergI.J. TrentC.M. SchulzeP.C. Lipid metabolism and toxicity in the heart.Cell Metab.201215680581210.1016/j.cmet.2012.04.006 22682221
    [Google Scholar]
  15. KolczynskaK. Loza-ValdesA. HawroI. SumaraG. Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.Lipids Health Dis.202019111310.1186/s12944‑020‑01286‑8 32466765
    [Google Scholar]
  16. FieldB.C. GordilloR. SchererP.E. The role of ceramides in diabetes and cardiovascular disease regulation of ceramides by adipokines.Front. Endocrinol. (Lausanne)20201156925010.3389/fendo.2020.569250 33133017
    [Google Scholar]
  17. PetersenM.C. ShulmanG.I. Mechanisms of insulin action and insulin resistance.Physiol. Rev.20189842133222310.1152/physrev.00063.2017 30067154
    [Google Scholar]
  18. KruszewskaJ. Cudnoch-JedrzejewskaA. CzarzastaK. Remodeling and fibrosis of the cardiac muscle in the course of obesity-pathogenesis and involvement of the extracellular matrix.Int. J. Mol. Sci.2022238419510.3390/ijms23084195 35457013
    [Google Scholar]
  19. Clemente-SuárezV.J. Redondo-FlórezL. Beltrán-VelascoA.I. The role of adipokines in health and disease.Biomedicines2023115129010.3390/biomedicines11051290 37238961
    [Google Scholar]
  20. BoucherJ. KleinriddersA. KahnC.R. Insulin receptor signaling in normal and insulin-resistant states.Cold Spring Harb. Perspect. Biol.201461a00919110.1101/cshperspect.a009191 24384568
    [Google Scholar]
  21. MeexR.C.R. BlaakE.E. van LoonL.J.C. Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes.Obes. Rev.20192091205121710.1111/obr.12862 31240819
    [Google Scholar]
  22. DabravolskiS.A. SadykhovN.K. KartuesovA.G. BorisovE.E. SukhorukovV.N. OrekhovA.N. The role of mitochondrial abnormalities in diabetic cardiomyopathy.Int. J. Mol. Sci.20222314786310.3390/ijms23147863 35887211
    [Google Scholar]
  23. BhargavaS.K. SinghT.G. MannanA. SinghS. SinghM. GuptaS. Pharmacological evaluation of Thuja occidentalis for the attenuation of neuropathy via AGEs and TNF-α inhibition in diabetic neuropathic rats.Environ. Sci. Pollut. Res. Int.20222940605426055710.1007/s11356‑022‑20106‑3 35420347
    [Google Scholar]
  24. BhargavaS.K. SinghT.G. MannanA. SinghS. GuptaS. Pharmacological evaluation of Thuja occidentalis for the attenuation of nephropathy in streptozotocin-induced diabetes rats.Obes. Med.20223110039110.1016/j.obmed.2022.100391
    [Google Scholar]
  25. KumarS. BehlT. SachdevaM. Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus.Life Sci.202126411866110.1016/j.lfs.2020.118661 33121986
    [Google Scholar]
  26. Lorenzo-AlmorósA. TuñónJ. OrejasM. CortésM. EgidoJ. LorenzoÓ. Diagnostic approaches for diabetic cardiomyopathy.Cardiovasc. Diabetol.20171612810.1186/s12933‑017‑0506‑x 28231848
    [Google Scholar]
  27. FangZ.Y. PrinsJ.B. MarwickT.H. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications.Endocr. Rev.200425454356710.1210/er.2003‑0012 15294881
    [Google Scholar]
  28. ChavaliV. TyagiS.C. MishraP.K. Predictors and prevention of diabetic cardiomyopathy.Diabetes Metab. Syndr. Obes.20136151160 23610527
    [Google Scholar]
  29. Falcão-PiresI. Leite-MoreiraA.F. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment.Heart Fail. Rev.201217332534410.1007/s10741‑011‑9257‑z 21626163
    [Google Scholar]
  30. XuG. ChenJ. JingG. ShalevA. Preventing β-cell loss and diabetes with calcium channel blockers.Diabetes201261484885610.2337/db11‑0955 22442301
    [Google Scholar]
  31. MeusserB. HirschC. JaroschE. SommerT. ERAD: the long road to destruction.Nat. Cell Biol.20057876677210.1038/ncb0805‑766 16056268
    [Google Scholar]
  32. JiaG. Whaley-ConnellA. SowersJ.R. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease.Diabetologia2018611212810.1007/s00125‑017‑4390‑4 28776083
    [Google Scholar]
  33. SunS. YangS. AnN. Astragalus polysaccharides inhibits cardiomyocyte apoptosis during diabetic cardiomyopathy via the endoplasmic reticulum stress pathway.J. Ethnopharmacol.201923811185710.1016/j.jep.2019.111857 30959142
    [Google Scholar]
  34. WuT. DongZ. GengJ. Valsartan protects against ER stress-induced myocardial apoptosis via CHOP/Puma signaling pathway in streptozotocin-induced diabetic rats.Eur. J. Pharm. Sci.201142549650210.1016/j.ejps.2011.02.005 21345370
    [Google Scholar]
  35. GuoR. LiuW. LiuB. ZhangB. LiW. XuY. SIRT1 suppresses cardiomyocyte apoptosis in diabetic cardiomyopathy: An insight into endoplasmic reticulum stress response mechanism.Int. J. Cardiol.2015191364510.1016/j.ijcard.2015.04.245 25965594
    [Google Scholar]
  36. YuH. ZhenJ. YangY. GuJ. WuS. LiuQ. Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in a streptozotocin-induced diabetes rat model.J. Cell. Mol. Med.201620462363110.1111/jcmm.12739 26869403
    [Google Scholar]
  37. KrebsJ. AgellonL.B. MichalakM. Ca2+ homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling.Biochem. Biophys. Res. Commun.2015460111412110.1016/j.bbrc.2015.02.004 25998740
    [Google Scholar]
  38. XuJ. ZhouQ. XuW. CaiL. Endoplasmic reticulum stress and diabetic cardiomyopathy.Exp. Diabetes Res.2012201282797110.1155/2012/827971
    [Google Scholar]
  39. Matuz-MaresD. González-AndradeM. Araiza-VillanuevaM.G. Vilchis-LanderosM.M. Vázquez-MezaH. Mitochondrial calcium: Effects of its imbalance in disease.Antioxidants202211580110.3390/antiox11050801 35624667
    [Google Scholar]
  40. BattiproluP.K. GilletteT.G. WangZ.V. LavanderoS. HillJ.A. Diabetic cardiomyopathy: mechanisms and therapeutic targets.Drug Discov. Today Dis. Mech.201072e135e14310.1016/j.ddmec.2010.08.001 21274425
    [Google Scholar]
  41. GollmerJ. ZirlikA. BuggerH. Established and emerging mechanisms of diabetic cardiomyopathy.J. Lipid Atheroscler.201981264710.12997/jla.2019.8.1.26 32821697
    [Google Scholar]
  42. PereiraL. MatthesJ. SchusterI. Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice.Diabetes200655360861510.2337/diabetes.55.03.06.db05‑1284 16505222
    [Google Scholar]
  43. TrostS.U. BelkeD.D. BluhmW.F. MeyerM. SwansonE. DillmannW.H. Overexpression of the sarcoplasmic reticulum Ca(2+)-ATPase improves myocardial contractility in diabetic cardiomyopathy.Diabetes20025141166117110.2337/diabetes.51.4.1166 11916940
    [Google Scholar]
  44. Al KuryL.T. Calcium homeostasis in ventricular myocytes of diabetic cardiomyopathy.J. Diabetes Res.202020201942086
    [Google Scholar]
  45. YoastR.E. EmrichS.M. ZhangX. The Mitochondrial Ca2+ uniporter is a central regulator of interorganellar Ca2+ transfer and NFAT activation.J. Biol. Chem.2021297410117410.1016/j.jbc.2021.101174 34499925
    [Google Scholar]
  46. LeeS.H. DuronH.E. ChaudhuriD. Beyond the TCA cycle: new insights into mitochondrial calcium regulation of oxidative phosphorylation.Biochem. Soc. Trans.20235141661167310.1042/BST20230012 37641565
    [Google Scholar]
  47. PattiM.E. CorveraS. The role of mitochondria in the pathogenesis of type 2 diabetes.Endocr. Rev.201031336439510.1210/er.2009‑0027 20156986
    [Google Scholar]
  48. DuncanJ.G. Mitochondrial dysfunction in diabetic cardiomyopathy.Biochim. Biophys. Acta Mol. Cell Res.2011181371351135910.1016/j.bbamcr.2011.01.014 21256163
    [Google Scholar]
  49. GargN. SinghT.G. KhanH. AroraS. KaurA. MannanA. Mechanistic interventions of selected ocimum species in management of diabetes, obesity and liver disorders: Transformative Developments from Preclinical to Clinical Approaches.Biointerface Res. Appl. Chem.20211211304132310.33263/BRIAC121.13041323
    [Google Scholar]
  50. JiaG. HillM.A. SowersJ.R. Diabetic cardiomyopathy.Circ. Res.2018122462463810.1161/CIRCRESAHA.117.311586 29449364
    [Google Scholar]
  51. BeheraR. SharmaV. GrewalA.K. Mechanistic correlation between mitochondrial permeability transition pores and mitochondrial ATP dependent potassium channels in ischemia reperfusion.Biomed. Pharmacother.202316211459910.1016/j.biopha.2023.114599 37004326
    [Google Scholar]
  52. ChenJ. ZhangZ. CaiL. Diabetic cardiomyopathy and its prevention by Nrf2: current status.Diabetes Metab. J.201438533734510.4093/dmj.2014.38.5.337 25349820
    [Google Scholar]
  53. CaiL. KleinJ.B. KangY.J. Metallothionein inhibits peroxynitrite-induced DNA and lipoprotein damage.J. Biol. Chem.200027550389573896010.1074/jbc.C000593200 11042194
    [Google Scholar]
  54. FyhrquistF. SaijonmaaO. Renin-angiotensin system revisited.J. Intern. Med.2008264322423610.1111/j.1365‑2796.2008.01981.x 18793332
    [Google Scholar]
  55. HuynhK. BernardoB.C. McMullenJ.R. RitchieR.H. Diabetic cardiomyopathy: Mechanisms and new treatment strategies targeting antioxidant signaling pathways.Pharmacol. Ther.2014142337541510.1016/j.pharmthera.2014.01.003 24462787
    [Google Scholar]
  56. LeeW.S. KimJ. Diabetic cardiomyopathy: where we are and where we are going.Korean J. Intern. Med. (Korean. Assoc. Intern. Med.)201732340442110.3904/kjim.2016.208 28415836
    [Google Scholar]
  57. BoudinaS. AbelE.D. Diabetic cardiomyopathy, causes and effects.Rev. Endocr. Metab. Disord.2010111313910.1007/s11154‑010‑9131‑7 20180026
    [Google Scholar]
  58. ManriqueC. LastraG. HabibiJ. Methods in the evaluation of cardiovascular renin angiotensin aldosterone activation and oxidative stress.Methods Mol. Med.200713916317910.1007/978‑1‑59745‑571‑8_10 18287671
    [Google Scholar]
  59. CooperS.A. Whaley-ConnellA. HabibiJ. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance.Am. J. Physiol. Heart Circ. Physiol.20072934H2009H202310.1152/ajpheart.00522.2007 17586614
    [Google Scholar]
  60. CatenaC. ColussiG. BrosoloG. Iogna-PratL. SechiL.A. Aldosterone and aldosterone antagonists in cardiac disease: what is known, what is new.Am. J. Cardiovasc. Dis.2012215057 22254214
    [Google Scholar]
  61. MandaviaC.H. AroorA.R. DeMarcoV.G. SowersJ.R. Molecular and metabolic mechanisms of cardiac dysfunction in diabetes.Life Sci.2013921160160810.1016/j.lfs.2012.10.028 23147391
    [Google Scholar]
  62. WestermannD. RutschowS. JägerS. Contributions of inflammation and cardiac matrix metalloproteinase activity to cardiac failure in diabetic cardiomyopathy: the role of angiotensin type 1 receptor antagonism.Diabetes200756364164610.2337/db06‑1163 17327431
    [Google Scholar]
  63. SyedA.A. RezaM.I. ShafiqM. Cissus quadrangularis extract mitigates diabetic cardiomyopathy by inhibiting RAAS activation, inflammation and oxidative stress.Biomarkers202227874375210.1080/1354750X.2022.2107703 35896310
    [Google Scholar]
  64. ByrneN.J. RajasekaranN.S. AbelE.D. BuggerH. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy.Free Radic. Biol. Med.202116931734210.1016/j.freeradbiomed.2021.03.046 33910093
    [Google Scholar]
  65. SinghR. FarooqS.A. MannanA. Animal models of diabetic microvascular complications: Relevance to clinical features.Biomed. Pharmacother.202214511230510.1016/j.biopha.2021.112305 34872802
    [Google Scholar]
  66. ZhangX. ChenC. A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy.Endocrine201241339840910.1007/s12020‑012‑9623‑1 22322947
    [Google Scholar]
  67. MannanA. GargN. SinghT.G. KangH.K. Peroxisome proliferator-activated receptor-gamma (PPAR-ɣ): Molecular effects and its importance as a novel therapeutic target for cerebral ischemic injury.Neurochem. Res.202146112800283110.1007/s11064‑021‑03402‑1 34282491
    [Google Scholar]
  68. HerreroP. PetersonL.R. McGillJ.B. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus.J. Am. Coll. Cardiol.200647359860410.1016/j.jacc.2005.09.030 16458143
    [Google Scholar]
  69. ParimB. Sathibabu UddandraoV.V. SaravananG. Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy.Heart Fail. Rev.201924227929910.1007/s10741‑018‑9749‑1 30349977
    [Google Scholar]
  70. AroraA. BehlT. SehgalA. Unravelling the involvement of gut microbiota in type 2 diabetes mellitus.Life Sci.202127311931110.1016/j.lfs.2021.119311 33662428
    [Google Scholar]
  71. AnD. RodriguesB. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy.Am. J. Physiol. Heart Circ. Physiol.20062914H1489H150610.1152/ajpheart.00278.2006 16751293
    [Google Scholar]
  72. VelezM. KohliS. SabbahH.N. Animal models of insulin resistance and heart failure.Heart Fail. Rev.201419111310.1007/s10741‑013‑9387‑6 23456447
    [Google Scholar]
  73. LeeT.I. KaoY.H. ChenY.C. HuangJ.H. HsiaoF.C. ChenY.J. Peroxisome proliferator-activated receptors modulate cardiac dysfunction in diabetic cardiomyopathy.Diabetes Res. Clin. Pract.2013100333033910.1016/j.diabres.2013.01.008 23369225
    [Google Scholar]
  74. BuggerH. AbelE.D. Molecular mechanisms of diabetic cardiomyopathy.Diabetologia201457466067110.1007/s00125‑014‑3171‑6 24477973
    [Google Scholar]
  75. BaevA.Y. VinokurovA.Y. NovikovaI.N. DreminV.V. PotapovaE.V. AbramovA.Y. Interaction of mitochondrial calcium and ROS in neurodegeneration.Cells202211470610.3390/cells11040706 35203354
    [Google Scholar]
  76. BhattiJ.S. BhattiG.K. ReddyP.H. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochimica et Biophysica Acta (BBA) -.Mol Basis Dis20171863510661077
    [Google Scholar]
  77. NishikawaT. EdelsteinD. DuX.L. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage.Nature2000404677978779010.1038/35008121 10783895
    [Google Scholar]
  78. ZorovD.B. JuhaszovaM. SollottS.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release.Physiol. Rev.201494390995010.1152/physrev.00026.2013 24987008
    [Google Scholar]
  79. TarquiniR. LazzeriC. PalaL. RotellaC.M. GensiniG.F. The diabetic cardiomyopathy.Acta Diabetol.201148317318110.1007/s00592‑010‑0180‑x 20198391
    [Google Scholar]
  80. ZhaoW. ZhaoT. ChenY. AhokasR.A. SunY. Oxidative stress mediates cardiac fibrosis by enhancing transforming growth factor-beta1 in hypertensive rats.Mol. Cell. Biochem.20083171-2435010.1007/s11010‑008‑9803‑8 18581202
    [Google Scholar]
  81. KaludercicN. Mialet-PerezJ. PaolocciN. PariniA. Di LisaF. Monoamine oxidases as sources of oxidants in the heart.J. Mol. Cell. Cardiol.201473344210.1016/j.yjmcc.2013.12.032 24412580
    [Google Scholar]
  82. MannanA. SinghT.G. SinghV. GargN. KaurA. SinghM. Insights into the mechanism of the therapeutic potential of herbal monoamine oxidase inhibitors in neurological diseases.Curr. Drug Targets202223328631010.2174/1389450122666210707120256 34238153
    [Google Scholar]
  83. NiR. CaoT. XiongS. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy.Free Radic. Biol. Med.201690122310.1016/j.freeradbiomed.2015.11.013 26577173
    [Google Scholar]
  84. UmbarkarP. SinghS. ArkatS. BodhankarS.L. LohidasanS. SitasawadS.L. Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy.Free Radic. Biol. Med.20158726327310.1016/j.freeradbiomed.2015.06.025 26122707
    [Google Scholar]
  85. DingW. FengH. LiW.J. Apocynin attenuates diabetic cardiomyopathy by suppressing ASK1-p38/JNK signaling.Eur. J. Pharmacol.202190917440210.1016/j.ejphar.2021.174402 34348125
    [Google Scholar]
  86. RajeshM. MukhopadhyayP. BátkaiS. Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathy.J. Cell. Mol. Med.2009138b2330234110.1111/j.1582‑4934.2008.00564.x 19175688
    [Google Scholar]
  87. JoH. OtaniH. JoF. Inhibition of nitric oxide synthase uncoupling by sepiapterin improves left ventricular function in streptozotocin-induced diabetic mice.Clin. Exp. Pharmacol. Physiol.201138848549310.1111/j.1440‑1681.2011.05535.x 21554376
    [Google Scholar]
  88. ToldoS. MezzaromaE. BuckleyL.F. Targeting the NLRP3 inflammasome in cardiovascular diseases.Pharmacol. Ther.202223610805310.1016/j.pharmthera.2021.108053 34906598
    [Google Scholar]
  89. SunY. DingS. NLRP3 Inflammasome in diabetic cardiomyopathy and exercise intervention.Int. J. Mol. Sci.202122241322810.3390/ijms222413228 34948026
    [Google Scholar]
  90. SwansonK.V. DengM. TingJ.P.Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics.Nat. Rev. Immunol.201919847748910.1038/s41577‑019‑0165‑0 31036962
    [Google Scholar]
  91. LuoB. HuangF. LiuY. NLRP3 Inflammasome as a molecular marker in diabetic cardiomyopathy.Front. Physiol.2017851910.3389/fphys.2017.00519 28790925
    [Google Scholar]
  92. DingK. SongC. HuH. YinK. HuangH. TangH. The role of NLRP3 inflammasome in diabetic cardiomyopathy and its therapeutic implications.Oxid. Med. Cell. Longev.2022202211910.1155/2022/3790721 36111168
    [Google Scholar]
  93. RobinsonN. GanesanR. HegedűsC. KovácsK. KuferT.A. VirágL. Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos.Redox Biol.20192610123910.1016/j.redox.2019.101239 31212216
    [Google Scholar]
  94. LuoB. LiB. WangW. NLRP3 gene silencing ameliorates diabetic cardiomyopathy in a type 2 diabetes rat model.PLoS One201498e10477110.1371/journal.pone.0104771 25136835
    [Google Scholar]
  95. YangF. QinY. WangY. Metformin inhibits the NLRP3 inflammasome via AMPK/mTOR-dependent effects in diabetic cardiomyopathy.Int. J. Biol. Sci.20191551010101910.7150/ijbs.29680 31182921
    [Google Scholar]
  96. LiX. LiZ. LiB. ZhuX. LaiX. Klotho improves diabetic cardiomyopathy by suppressing the NLRP3 inflammasome pathway.Life Sci.201923411677310.1016/j.lfs.2019.116773 31422095
    [Google Scholar]
  97. LuoB. LiB. WangW. Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model.Cardiovasc. Drugs Ther.2014281334310.1007/s10557‑013‑6498‑1 24254031
    [Google Scholar]
  98. WangY. LiH. LiY. Coriolus versicolor alleviates diabetic cardiomyopathy by inhibiting cardiac fibrosis and NLRP3 inflammasome activation.Phytother. Res.201933102737274810.1002/ptr.6448 31338905
    [Google Scholar]
  99. SunX. SunX. MengH. Krill oil inhibits NLRP3 inflammasome activation in the prevention of the pathological injuries of diabetic cardiomyopathy.Nutrients202214236810.3390/nu14020368 35057549
    [Google Scholar]
  100. ZhangH. ChenX. ZongB. Gypenosides improve diabetic cardiomyopathy by inhibiting ROS-mediated NLRP 3 inflammasome activation.J. Cell. Mol. Med.20182294437444810.1111/jcmm.13743 29993180
    [Google Scholar]
  101. Soares-SilvaM. DinizF.F. GomesG.N. BahiaD. The mitogen-activated protein kinase (MAPK) pathway: Role in immune evasion by trypanosomatids.Front. Microbiol.2016718310.3389/fmicb.2016.00183 26941717
    [Google Scholar]
  102. DhimanS. MannanA. TanejaA. MohanM. SinghT.G. Sirtuin dysregulation in Parkinson’s disease: Implications of acetylation and deacetylation processes.Life Sci.202434212253710.1016/j.lfs.2024.122537 38428569
    [Google Scholar]
  103. ZhangW. LiuH.T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells.Cell Res.200212191810.1038/sj.cr.7290105 11942415
    [Google Scholar]
  104. AvagimyanA. PopovS. ShalnovaS. The pathophysiological basis of diabetic cardiomyopathy development.Curr. Probl. Cardiol.202247910115610.1016/j.cpcardiol.2022.101156 35192869
    [Google Scholar]
  105. XuZ. SunJ. TongQ. The role of ERK1/2 in the development of diabetic cardiomyopathy.Int. J. Mol. Sci.20161712200110.3390/ijms17122001 27941647
    [Google Scholar]
  106. AdhikaryL. ChowF. Nikolic-PatersonD.J. Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy.Diabetologia20044771210122210.1007/s00125‑004‑1437‑0 15232685
    [Google Scholar]
  107. WestermannD. RutschowS. Van LinthoutS. Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus.Diabetologia200649102507251310.1007/s00125‑006‑0385‑2 16937126
    [Google Scholar]
  108. WangS. DingL. JiH. XuZ. LiuQ. ZhengY. The role of p38 MAPK in the development of diabetic cardiomyopathy.Int. J. Mol. Sci.2016177103710.3390/ijms17071037 27376265
    [Google Scholar]
  109. Van LinthoutS. RiadA. DhayatN. Anti-inflammatory effects of atorvastatin improve left ventricular function in experimental diabetic cardiomyopathy.Diabetologia20075091977198610.1007/s00125‑007‑0719‑8 17589825
    [Google Scholar]
  110. FanZ. DongJ. MuY. LiuX. Nesfatin-1 protects against diabetic cardiomyopathy in the streptozotocin-induced diabetic mouse model via the p38-MAPK pathway.Bioengineered2022136146701468110.1080/21655979.2022.2066748 35818327
    [Google Scholar]
  111. WangY. Inhibition of JNK by novel curcumin analog C66 prevents diabetic cardiomyopathy with a preservation of cardiac metallothionein expression.Am. J. Physiol. Endocrinol. Metab.201430611E1239E1247
    [Google Scholar]
  112. MarroccoV. BogomolovasJ. EhlerE. PKC and PKN in heart disease.J. Mol. Cell. Cardiol.201912821222610.1016/j.yjmcc.2019.01.029 30742812
    [Google Scholar]
  113. NewtonA.C. AntalC.E. SteinbergS.F. Protein kinase C mechanisms that contribute to cardiac remodelling.Clin. Sci. (Lond.)2016130171499151010.1042/CS20160036 27433023
    [Google Scholar]
  114. SinghR.M. Protein kinase C and cardiac dysfunction: a review.Heart Fail. Rev.201722843859
    [Google Scholar]
  115. GeraldesP. KingG.L. Activation of protein kinase C isoforms and its impact on diabetic complications.Circ. Res.201010681319133110.1161/CIRCRESAHA.110.217117 20431074
    [Google Scholar]
  116. GiaccoF. BrownleeM. Oxidative stress and diabetic complications.Circ. Res.201010791058107010.1161/CIRCRESAHA.110.223545 21030723
    [Google Scholar]
  117. WayK.J. IsshikiK. SuzumaK. Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2 activation and diabetes.Diabetes20025192709271810.2337/diabetes.51.9.2709 12196463
    [Google Scholar]
  118. LeiS. LiH. XuJ. Hyperglycemia-induced protein kinase C β2 activation induces diastolic cardiac dysfunction in diabetic rats by impairing caveolin-3 expression and Akt/eNOS signaling.Diabetes20136272318232810.2337/db12‑1391 23474486
    [Google Scholar]
  119. ConnellyK.A. KellyD.J. ZhangY. Inhibition of protein kinase C-beta by ruboxistaurin preserves cardiac function and reduces extracellular matrix production in diabetic cardiomyopathy.Circ. Heart Fail.20092212913710.1161/CIRCHEARTFAILURE.108.765750 19808328
    [Google Scholar]
  120. SoetiknoV. SariF.R. SukumaranV. Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC-MAPK signaling pathway.Eur. J. Pharm. Sci.201247360461410.1016/j.ejps.2012.04.018 22564708
    [Google Scholar]
  121. BagulP.K. Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3.J. Nutr. Biochem.201526
    [Google Scholar]
  122. ValenG. Nuclear factor kappa-B and the heart.J. Am. Coll. Cardiol.200138
    [Google Scholar]
  123. MohanM. MannanA. SinghT.G. Therapeutic implication of Sonic Hedgehog as a potential modulator in ischemic injury.Pharmacol. Rep.202375483886010.1007/s43440‑023‑00505‑0 37347388
    [Google Scholar]
  124. SinghS. SinghT.G. Role of nuclear factor kappa B (NF-κB) signalling in neurodegenerative diseases: An mechanistic approach.Curr. Neuropharmacol.2020181091893510.2174/1570159X18666200207120949 32031074
    [Google Scholar]
  125. MinW. BinZ.W. QuanZ.B. HuiZ.J. ShengF.G. The signal transduction pathway of PKC/NF-κB/c-fos may be involved in the influence of high glucose on the cardiomyocytes of neonatal rats.Cardiovasc. Diabetol.200981810.1186/1475‑2840‑8‑8 19210763
    [Google Scholar]
  126. MazièreC. MazièreJ.C. Activation of transcription factors and gene expression by oxidized low-density lipoprotein.Free Radic. Biol. Med.200946212713710.1016/j.freeradbiomed.2008.10.024 18996472
    [Google Scholar]
  127. RicoteM. LiA.C. WillsonT.M. KellyC.J. GlassC.K. The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation.Nature19983916662798210.1038/34178 9422508
    [Google Scholar]
  128. LiH. MalhotraS. KumarA. Nuclear factor-kappa B signaling in skeletal muscle atrophy.J. Mol. Med. (Berl.)200886101113112610.1007/s00109‑008‑0373‑8 18574572
    [Google Scholar]
  129. BrownK.D. ClaudioE. SiebenlistU. The roles of the classical and alternative nuclear factor-kappaB pathways: potential implications for autoimmunity and rheumatoid arthritis.Arthritis Res. Ther.200810421210.1186/ar2457 18771589
    [Google Scholar]
  130. MatsukuraS. KokubuF. KurokawaM. Synthetic double‐stranded RNA induces multiple genes related to inflammation through Toll-like receptor 3 depending on NF-κB and/or IRF‐3 in airway epithelial cells.Clin. Exp. Allergy20063681049106210.1111/j.1365‑2222.2006.02530.x 16911361
    [Google Scholar]
  131. JiaG. DeMarcoV.G. SowersJ.R. Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy.Nat. Rev. Endocrinol.201612314415310.1038/nrendo.2015.216 26678809
    [Google Scholar]
  132. MariappanN. ElksC.M. SriramulaS. NF-κB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes.Cardiovasc. Res.201085347348310.1093/cvr/cvp305 19729361
    [Google Scholar]
  133. HjL. YlF. HhL. Apigenin alleviates STZ-induced diabetic cardiomyopathy.Mol. Cell. Biochem.2017428921
    [Google Scholar]
  134. AlshehriA.S. El-KottA.F. EleawaS.M. Kaempferol protects against streptozotocin-induced diabetic cardiomyopathy in rats by a hypoglycemic effect and upregulating SIRT1.J. Physiol. Pharmacol.202172372 34810287
    [Google Scholar]
  135. LeveltE. GulsinG. NeubauerS. McCannG.P. Mechanisms in endocrinology: Diabetic cardiomyopathy: pathophysiology and potential metabolic interventions state of the art review.Eur. J. Endocrinol.20181784R127R13910.1530/EJE‑17‑0724 29440374
    [Google Scholar]
  136. BorghettiG. von LewinskiD. EatonD.M. SourijH. HouserS.R. WallnerM. Diabetic cardiomyopathy: Current and future therapies. Beyond glycemic control.Front. Physiol.20189151410.3389/fphys.2018.01514 30425649
    [Google Scholar]
  137. MurtazaG. VirkH.U.H. KhalidM. Diabetic cardiomyopathy - A comprehensive updated review.Prog. Cardiovasc. Dis.201962431532610.1016/j.pcad.2019.03.003 30922976
    [Google Scholar]
  138. BerezinA.E. BerezinA.A. Circulating cardiac biomarkers in diabetes mellitus: A new dawn for risk stratification-a narrative review.Diabetes Ther.20201161271129110.1007/s13300‑020‑00835‑9 32430864
    [Google Scholar]
  139. AbdelrahmanA.H. SalamaI.I. SalamaS.I. Role of some serum biomarkers in the early detection of diabetic cardiomyopathy.Future Sci. OA202175FSO68210.2144/fsoa‑2020‑0184 34046187
    [Google Scholar]
  140. KumarM. DevS. KhalidM.U. The bidirectional link between diabetes and kidney disease: mechanisms and management.Cureus2023159e4561510.7759/cureus.45615 37868469
    [Google Scholar]
  141. PergolaV. CabrelleG. MattesiG. Added value of CCTA-derived features to predict MACEs in stable patients undergoing coronary computed tomography.Diagnostics (Basel)2022126144610.3390/diagnostics12061446 35741256
    [Google Scholar]
  142. TassettiL. SfrisoE. TorloneF. The role of multimodality imaging (CT & MR) as a guide to the management of chronic coronary syndromes.J. Clin. Med.20241312345010.3390/jcm13123450 38929984
    [Google Scholar]
  143. SperlonganoS. D’AndreaA. MeleD. Left ventricular deformation and vortex analysis in heart failure: From ultrasound technique to current clinical application.Diagnostics (Basel)202111589210.3390/diagnostics11050892 34067703
    [Google Scholar]
  144. JmP. GiV. Diabetic cardiomyopathy: Pathophysiology, diagnostic evaluation and management.World J. Diabetes20134
    [Google Scholar]
  145. MordiI.R. Non-invasive imaging in diabetic cardiomyopathy.J. Cardiovasc. Dev. Dis.2019621810.3390/jcdd6020018 30995812
    [Google Scholar]
  146. YoussefM.E. El-AzabM.F. Abdel-DayemM.A. YahyaG. AlanaziI.S. SaberS. Electrocardiographic and histopathological characterizations of diabetic cardiomyopathy in rats.Environ. Sci. Pollut. Res. Int.20222917257232573210.1007/s11356‑021‑17831‑6 34845640
    [Google Scholar]
  147. MayaL. VillarrealF.J. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis.J. Mol. Cell. Cardiol.201048352452910.1016/j.yjmcc.2009.06.021 19595694
    [Google Scholar]
  148. SassoF.C. RambaldiP.F. CarbonaraO. Perspectives of nuclear diagnostic imaging in diabetic cardiomyopathy.Nutr. Metab. Cardiovasc. Dis.201020320821610.1016/j.numecd.2009.08.013 19939648
    [Google Scholar]
  149. KumricM. Ticinovic KurirT. BorovacJ.A. BozicJ. Role of novel biomarkers in diabetic cardiomyopathy.World J. Diabetes202112668570510.4239/wjd.v12.i6.685 34168722
    [Google Scholar]
  150. KodamaS. TanakaS. HeianzaY. Association between physical activity and risk of all-cause mortality and cardiovascular disease in patients with diabetes: a meta-analysis.Diabetes Care201336247147910.2337/dc12‑0783 23349151
    [Google Scholar]
  151. HordernM.D. CoombesJ.S. CooneyL.M. JeffriessL. PrinsJ.B. MarwickT.H. Effects of exercise intervention on myocardial function in type 2 diabetes.Heart200995161343134910.1136/hrt.2009.165571 19429570
    [Google Scholar]
  152. SivasankarD. GeorgeM. SriramD.K. Novel approaches in the treatment of diabetic cardiomyopathy.Biomed. Pharmacother.20181061039104510.1016/j.biopha.2018.07.051 30119169
    [Google Scholar]
  153. VaccaroO. MasulliM. BonoraE. Addition of either pioglitazone or a sulfonylurea in type 2 diabetic patients inadequately controlled with metformin alone: Impact on cardiovascular events. A randomized controlled trial.Nutr. Metab. Cardiovasc. Dis.20122211997100610.1016/j.numecd.2012.09.003 23063367
    [Google Scholar]
  154. GrimmD. JabuschH.C. KossmehlP. Experimental diabetes and left ventricular hypertrophy.Cardiovasc. Pathol.200211422923710.1016/S1054‑8807(01)00116‑8 12140129
    [Google Scholar]
  155. DeedwaniaP.C. GilesT.D. KlibanerM. Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: Experiences from MERIT-HF.Am. Heart J.2005149115916710.1016/j.ahj.2004.05.056 15660048
    [Google Scholar]
  156. ShahA.M. ShinS.H. TakeuchiM. Left ventricular systolic and diastolic function, remodelling, and clinical outcomes among patients with diabetes following myocardial infarction and the influence of direct renin inhibition with aliskiren.Eur. J. Heart Fail.201214218519210.1093/eurjhf/hfr125 21965526
    [Google Scholar]
  157. KawasakiD. KosugiK. WakiH. YamamotoK. TsujinoT. MasuyamaT. Role of activated renin-angiotensin system in myocardial fibrosis and left ventricular diastolic dysfunction in diabetic patients--reversal by chronic angiotensin II type 1A receptor blockade.Circ. J.200771452452910.1253/circj.71.524 17384453
    [Google Scholar]
  158. IsfortM. StevensS.C.W. SchafferS. JongC.J. WoldL.E. Metabolic dysfunction in diabetic cardiomyopathy.Heart Fail. Rev.2014191354810.1007/s10741‑013‑9377‑8 23443849
    [Google Scholar]
  159. TateM. GrieveD.J. RitchieR.H. Are targeted therapies for diabetic cardiomyopathy on the horizon?Clin. Sci. (Lond.)20171311089791510.1042/CS20160491 28473471
    [Google Scholar]
  160. Al-RasheedN.M. Al-RasheedN.M. HasanI.H. Simvastatin ameliorates diabetic cardiomyopathy by attenuating oxidative stress and inflammation in rats.Oxid. Med. Cell. Longev.201720171109201510.1155/2017/1092015 29138670
    [Google Scholar]
  161. Ewang-EmukowhateM. WierzbickiA.S. Lipid-lowering agents.J. Cardiovasc. Pharmacol. Ther.201318540141110.1177/1074248413492906 23811423
    [Google Scholar]
  162. CarillionA. FeldmanS. NaN. Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy.PLoS One2017127e018010310.1371/journal.pone.0180103 28727746
    [Google Scholar]
  163. JiaW. BaiT. ZengJ. Combined administration of metformin and atorvastatin attenuates diabetic cardiomyopathy by inhibiting inflammation, apoptosis, and oxidative stress in type 2 diabetic mice.Front. Cell Dev. Biol.2021963490010.3389/fcell.2021.634900 33718370
    [Google Scholar]
  164. HayatS.A. PatelB. KhattarR.S. MalikR.A. Diabetic cardiomyopathy: mechanisms, diagnosis and treatment.Clin. Sci. (Lond.)2004107653955710.1042/CS20040057 15341511
    [Google Scholar]
/content/journals/ccr/10.2174/011573403X331870241025094307
Loading
/content/journals/ccr/10.2174/011573403X331870241025094307
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test