Yousry, M., Alghandour, S. (2024). The Potential Ameliorative Effect of Empagliflozin on Myocardium in Cardiorenal Syndrome 3 via Targeting Mitophagy and Mitochondrial Biogenesis in Adult Male Albino Rat Model: Biochemical, Histological and Immunohistochemical Study. test, 5(2), 7-45. doi: 10.21608/ejmr.2024.239826.1468
Marwa Mohamed Yousry; Sarah Mohammed Alghandour. "The Potential Ameliorative Effect of Empagliflozin on Myocardium in Cardiorenal Syndrome 3 via Targeting Mitophagy and Mitochondrial Biogenesis in Adult Male Albino Rat Model: Biochemical, Histological and Immunohistochemical Study". test, 5, 2, 2024, 7-45. doi: 10.21608/ejmr.2024.239826.1468
Yousry, M., Alghandour, S. (2024). 'The Potential Ameliorative Effect of Empagliflozin on Myocardium in Cardiorenal Syndrome 3 via Targeting Mitophagy and Mitochondrial Biogenesis in Adult Male Albino Rat Model: Biochemical, Histological and Immunohistochemical Study', test, 5(2), pp. 7-45. doi: 10.21608/ejmr.2024.239826.1468
Yousry, M., Alghandour, S. The Potential Ameliorative Effect of Empagliflozin on Myocardium in Cardiorenal Syndrome 3 via Targeting Mitophagy and Mitochondrial Biogenesis in Adult Male Albino Rat Model: Biochemical, Histological and Immunohistochemical Study. test, 2024; 5(2): 7-45. doi: 10.21608/ejmr.2024.239826.1468

The Potential Ameliorative Effect of Empagliflozin on Myocardium in Cardiorenal Syndrome 3 via Targeting Mitophagy and Mitochondrial Biogenesis in Adult Male Albino Rat Model: Biochemical, Histological and Immunohistochemical Study

Egyptian Journal of Medical Research
Volume 5, Issue 2, April 2024, Pages 7-45    PDF (2.52 M)
Document Type: Original Article
DOI: 10.21608/ejmr.2024.239826.1468
Authors
Marwa Mohamed Yousry* 1; Sarah Mohammed Alghandour2
1Histology Department Faculty of Medicine Cairo University, Cairo, Egypt
2Histology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
Abstract
Background: Cardiorenal syndrome-3 (CRS3) represents the pathological link between kidneys and heart where acute kidney injury (AKI) causes serious cardiac abnormalities. Disrupted mitochondrial dynamics are the main contributor to CRS3. Mitophagy plays a protective role through reducing mitochondrial damage and oxidative-stress. Empagliflozin (EMPA), a sodium-glucose cotransporter-2 inhibitor, has therapeutic effects on cardiac and renal pathology with or without diabetes type-2 through anti-oxidative, anti-inflammatory &anti-apoptotic mechanisms. Aim of work: Evaluating EMPA probable reparative impact on the myocardium of adult male albino rat CRS3-model using biochemical, histological &immunohistochemical studies. Materials and Methods: Twenty-eight adult male albino rats (3months old, 200g weight) were divided into: control &experimental (subjected to AKI) groups. AKI-rats were subdivided equally into 3 subgroups, AKI, AKI/recovery &AKI/EMPA (received daily oral 20mg/kg EMPA 1week after renal surgery for 3weeks). Results: AKI induced a significant rise in serum urea, creatinine, cardiac TNF-α, H2O2 levels, P62, cytochrome-C area percentage, besides a non-significant increase in Mn-SOD level, mitophagy-PINK1/PARKIN &mitochondrial biogenesis-PGC1α gene expression, LC3B, sirtuin-3 area percentage &a significant decrease in ATP level. Myocardium showed darkly stained shrunken nuclei, disrupted transverse striations by H&E stain and minimal collagen deposition by Masson’s trichrome. AKI/recovery recorded further reduction in ATP, Mn-SOD levels, PINK1/PARKIN, PGC1α expression, LC3B, sirtuin-3 area percentage and evident increase in H2O2 level, P62, cytochrome-C area percentage with marked myocardial affection &more collagen deposition. AKI/EMPA demonstrated an obvious improvement in the previously mentioned results. Conclusion: EMPA ameliorated CRS3-induced myocardial damage through the inhibition of inflammation &mitochondrial oxidative-stress in addition to mitophagy &mitochondrial biogenesis activation. 
Keywords
Cardiorenal syndrome 3; mitophagy-mitochondrial biogenesis; LC3B; P62; EMPA
References

  1. Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, Lerma EV, Mezue K, Molitch M, Mullens W, Ronco C, Tang WHW, McCullough PA; American Heart Association Council on the Kidney in Cardiovascular Disease and Council on Clinical Cardiology. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement from the American Heart Association. Circulation. 2019;139: e840-e878.
  2. Lullo DL, Reeves RB, Bellasi A, Ronco C. Cardiorenal Syndrome in Acute Kidney Injury. Semin. Nephrol. 2019; 39: 31–40.
  3. Wang J, Toan S, Li R, Zhou H. Melatonin fine-tunes intracellular calcium signals and eliminates myocardial damage through the IP3R/MCU pathways in cardiorenal syndrome type 3. Biochemical Pharmacology. 2020; 174: Article ID 113832, 1-10.
  4. Wang J, Sun X, Wang X, Cui S, Liu R, Liu J, Fu B, Gong M, Wang C, Shi Y, Chen Q, Cai G, Chen X. Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway. Frontiers in Cell and Developmental Biology. 2021; 9: Article ID 630412, 1-15.
  5. Du Y, Li X, Liu B. Advances in pathogenesis and current therapeutic strategies for cardiorenal syndrome. Life Sciences. 2014;99: 1–6.
  6. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL, Sideris DP, Fogel AI, Youle RJ. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015; 524:309-314.
  7. Dorn GW. Parkin-dependent mitophagy in the heart. J. Mol. Cell. Cardiol. 2016; 95, 42–49.
  8. Riley BE, Lougheed JC, Callaway K, Velasquez M, Brecht E, Nguyen L, Shaler T, Walker D, Yang Y, Regnstrom K, Diep L, Zhang Z, Chiou S, Bova M, Artis DR, Yao N, Baker J, Yednock T, Johnston JA. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat Commun. 2013; 4: Article ID 1982,1-9.
  9. Rojansky R, Cha MY, Chan DC. Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. Elife. 2016;5: Article ID e17896,1-18.
  10. Livingston MJ, Wang J, Zhou J, Wu G, Ganley IG, Hill JA, Yin XM, Dong Z. Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys. Autophagy. 2019; 15:2142-2162.
  11. Tang C, Han H, Yan M, Zhu S, Liu J, Liu Z, He L, Tan J, Liu Y, Liu H, Sun L, Duan S, Peng Y, Liu F, Yin XM, Zhang Z, Dong Z. PINK1-PRKN/PARK2 pathway of mitophagy is activated to protect against renal ischemia-reperfusion injury. Autophagy. 2018; 14:880-897.
  12. Wang Y, Tang C, Cai J, Chen G, Zhang D, Zhang Z, Dong Z. PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect against kidney injury. Cell Death Dis. 2018; 9: Article ID 1113,1-14.
  13. Wang S, Chen Y, Li X, Zhang W, Liu Z, Wu M, Pan Q, Liu H. Emerging role of transcription factor EB in mitochondrial quality control. Biomed Pharmacother. 2020; 128: Article ID 110272,1-10.
  14. Karamanlidis G, Nascimben L, Couper GS, Shekar PS. del Monte F, Tian R. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res. 2010; 106:1541–1548.
  15. Dominy JE, Puigserver P. Mitochondrial biogenesis through activation of nuclear signaling proteins. Cold Spring Harb Perspect Biol. 2013; 5: Article ID a015008,1-18.
  16. Wang Y, Zhu J, Liu Z, Shu S, Fu Y, Liu Y, Cai J, Tang C, Liu Y, Yin X, Dong Z. The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury. Redox Biol. 2021; 38: Article ID 101767,1-16. 
  17. Wang C, Wang Y, Shen L. Mitochondrial proteins in heart failure: the role of deacetylation by SIRT3. Pharmacol Res. 2021;172: Article ID 105802, 1-12.
  18. Koentges C, Pfeil K, Schnick T, Wiese S, Dahlbock R, Cimolai MC, Meyer-Steenbuck M, Cenkerova K, Hoffmann MM, Jaeger C, Odening KE, Kammerer B, Hein L, Bode C, Bugger H. SIRT3 deficiency impairs mitochondrial and contractile function in the heart. Basic Res Cardiol. 2015; 110: Article ID 36,1-20.
  19. Li Y, Ma Y, Song L, Yu L, Zhang L, Zhang Y, Xing Y, Yin Y, Ma H. SIRT3 deficiency exacerbates p53/Parkin ‑ mediated mitophagy inhibition and promotes mitochondrial dysfunction: implication for aged hearts. Int J Mol Med. 2018; 41: 3517- 3526.
  20. Morigi M, Perico L, Benigni A. Sirtuins in renal health and disease. J Am Soc Nephrol. 2018; 29: 1799- 1809.
  21. Liu J, Li D, Zhang T, Tong Q, Ye RD, Lin L. SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity. Cell Death Dis. 2017;8: Article ID e3158, 1-11.
  22. Thomas MC, Cherney DZI. The actions of SGLT2 inhibitors on metabolism, renal function and blood pressure. Diabetologia. 2018; 61: 2098–2107.
  23. Martens P, Mathieu C, Verbrugge FH. Promise of SGLT2 inhibitors in heart failure: diabetes and beyond. Curr Treat Options Cardiovasc Med 2017; 19: Article ID 23,1-14.
  24. Chen J, Fan F, Wang JY, Long Y, Gao CL, Stanton RC, Xu Y. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis. Sci Rep. 2017; 7: Article ID 44128,1-9.
  25. Yurista SR, Silljé HHW, Oberdorf-Maass SU, Schouten EM, Pavez Giani MG, Hillebrands JL, van Goor H, van Veldhuisen DJ, de Boer RA, Westenbrink BD. Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in nondiabetic rats with left ventricular dysfunction after myocardial infarction. Eur J Heart Fail 2019; 21:862–873.
  26. Steven S, Oelze M, Hanf A, Kröller-Schön S, Kashani F, Roohani S, Welschof P, Kopp M, Gödtel-Armbrust U, Xia N, Li H, Schulz E, Lackner KJ, Wojnowski L, Bottari SP, Wenzel P, Mayoux E, Münzel T, Daiber A. The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats. Redox Biol. 2017; 13:370-385.
  27. Al-Jobori H, Daniele G, Cersosimo E, Triplitt C, Mehta R, Norton L, DeFronzo RA, Abdul-Ghani M. Empagliflozin and kinetics of renal glucose 2 transport in healthy individuals and individuals with type 2 diabetes. Diabetes.2017; 66:1999–2006.
  28. Hu Z, Ju F, Du L, Abbott GW. Empagliflozin protects the heart against ischemia/reperfusion-induced sudden cardiac death. Cardiovasc Diabetol. 2021; 20: Article ID 199,1-13. 
  29. Caio-SilvaW, da Silva Dias D, Junho CVC, Panico K, Neres-Santos RS, Pelegrino MT, Pieretti JC, Seabra AB, De Angelis K, Carneiro-Ramos MS. Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3. BioMed Res. Int. 2020; 2020: Article ID 1605358,1-11.
  30. Lima NKS, Farias WRA, Cirilo MAS, Oliveira AG, Farias JS, Aires RS, Muzi-Filho H, Paixão ADO, Vieira LD. Renal ischemia-reperfusion leads to hypertension and changes in proximal tubule Na+transport and renin-angiotensin-aldosterone system: Role of NADPH oxidase. Life Sci. 2021; 266: Article ID 118879,1-9.
  31. Pechman KR, De Miguel C, Lund H, Leonard EC, Basile DP, Mattson DL. Recovery from renal ischemia-reperfusion injury is associated with altered renal hemodynamics, blunted pressure natriuresis, and sodium-sensitive hypertension. Am J Physiol Regul Integr Comp Physiol. 2009; 297: R1358-R1363.
  32. El Agaty SM. Cardioprotective effect of vitamin D2 on isoproterenol-induced myocardial infarction in diabetic rats. Archives of Physiology and Biochemistry. 2019; 125:210- 219.
  33. Gumustaz K, Tanrived T, Kulaksiz I, Kafadar AM, Sanus GZ, Atukeren P, Kaynar MY. Cytochrome oxidase activity and ATP levels in high-grade gliomas and meningiomas. Turk Neurosurg. 2006;16: 64.
  34. L i S, Lin Q, Shao X, Zhu X, Wu J, Wu B, Zhang M, Zhou W, Zhou Y, Jin H, Zhang Z, Qi C, Shen J, Mou S, Gu L, Ni Z. Drp1-regulated PARK2-dependent mitophagy protects against renal fibrosis in unilateral ureteral obstruction. Free Radic Biol Med. 2020; 152:632-649.
  35. Suvarna K, Layton C, Bancroft J. The haematoxylins and eosin, Connective and mesenchymal tissue with their stains & Immunohistochemical and immunofluorescent techniques. In Bancroft's Theory and Practice of Histological Techniques (Eighth Edition), Elsevier, 2019, pp: 126-138, 153-175 & 337-394.
  36. Liu JX, Yang C, Zhang WH, Su HY, Liu ZJ, Pan Q, Liu HF. Disturbance of mitochondrial dynamics and mitophagy in sepsis-induced acute kidney injury. Life sciences. 2019; 235: Article ID 116828,1-9.
  37. Doi K. Kidney-Heart Interactions in Acute Kidney Injury. Nephron 2016; 134:141–144.
  38. Emsley R, Dunn G and White IR. Mediation and moderation of treatment effects in randomized controlled trials of complex interventions. Statistical Methods in Medical Research; 2010;19: 237-270.
  39. Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Polydatin inhibits mitochondrial dysfunction in the renal tubular epithelial cells of a rat model of sepsis-induced acute kidney injury. Anesth. Analg. 2015; 121: 1251–1260.
  40. Benck U, Schnuelle P, Krüger B, Nowak K, Riester T, Mundt H, Lutz N, Jung M, Birck R, Krämer BK, Schmitt WH. Excellent graft and patient survival after renal transplantation from donors after brain death with acute kidney injury: A case-control study. Int. Urol. Nephrol. 2015; 47: 2039–2046.
  41. Zhu YB, Zhang YP, Zhang J, Zhang YB. Evaluation of Vitamin C supplementation on kidney function and vascular reactivity following renal ischemic injury in mice. Kidney Blood Press. Res. 2016; 41: 460–470.
  42. Sawhney S, Marks A, Fluck N, Levin A, Prescott G, Black C. Intermediate and Long-term Outcomes of Survivors of Acute Kidney Injury Episodes: A Large Population-Based Cohort Study. Am. J. Kidney Dis. 2017; 69: 18–28.
  43. Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012; 81: 942–948.
  44. Wijerathne CUB, Madduma Hewage S, Siow YL, O K. Kidney Ischemia-Reperfusion Decreases Hydrogen Sulfide and Increases Oxidative Stress in the Heart. Biomolecules. 2020; 10: Article ID 1565,1-13. 
  45. Clementi A, Virzì GM, Brocca A, de Cal M, Pastori S, Clementi M, Granata A, Vescovo G, Ronco C. Advances in the pathogenesis of cardiorenal syndrome type 3. Oxid Med Cell Longev. 2015; 2015: Article ID 148082,1-8.
  46. Zhang X, Agborbesong E, Li X. The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential. Int. J. Mol. Sci. 2021; 22: Article ID 11253,1-22.
  47. Bhargava P, Schnellmann R.G. Mitochondrial energetics in the kidney. Nat. Rev. Nephrol. 2017; 13: 629–646.
  48. Ryczkowska K, Adach W, Janikowski K, Banach M, Bielecka-Dabrowa A. Menopause and women's cardiovascular health: is it really an obvious relationship? Arch Med Sci. 2022; 19:458-466.
  49. Neres-Santos RS, Junho CVC, Panico K, Caio-Silva W, Pieretti JC, Tamashiro JA, Seabra AB, Ribeiro CAJ, Carneiro-Ramos MS. Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C. Cells. 2021; Article ID 10:3029,1-14.
  50. Junho CVC, González-Lafuente L, Neres-Santos RS, Navarro-García JA, Rodríguez-Sánchez E, Ruiz-Hurtado G, Carneiro-Ramos MS. Klotho relieves inflammation and exerts a cardioprotective effect during renal ischemia/reperfusion-induced cardiorenal syndrome. Biomed Pharmacother. 2022; 153: Article ID 113515,1-13. 
  51. Falconi CA, Junho CVDC, Fogaça-Ruiz F, Vernier ICS, da Cunha RS, Stinghen AEM, Carneiro-Ramos. Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System. Frontiers in physiology. 2021; 12: Article ID 686249,1-20.
  52. Husain-Syed F, Rosner MH, Ronco C. Distant organ dysfunction in acute kidney injury. Acta Physiol.2020; 228: Article ID e13357,1-10.
  53. Tanriover C, Copur S, Ucku D, Cakir AB, Hasbal NB, Soler MJ, Kanbay M. The Mitochondrion: A Promising Target for Kidney Disease. Pharmaceutics. 2023; 15: Article ID 570,1-30. 
  54. Cai C, Wu F, Zhuang B, Ou Q, Peng X, Shi N, Peng L, Li Z, Wang J, Cai S, Tan Y. Empagliflozin activates Wnt/β-catenin to stimulate FUNDC1-dependent mitochondrial quality surveillance against type-3 cardiorenal syndrome. Mol Metab. 2022; 64: Article ID 101553,1-14.
  55. Moris D, Spartalis M, Spartalis E, Karachaliou GS, Karaolanis GI, Tsourouflis G, Tsilimigras DI, Tzatzaki E, Theocharis S. The role of reactive oxygen species in the pathophysiology of cardiovascular diseases and the clinical significance of myocardial redox. Ann Transl Med. 2017; 5: Article ID 326,1-10.
  56. Rubattu S, Mennuni S, Testa M, Mennuni M, Pierelli G, Pagliaro B, Gabriele E, Coluccia R, Autore C, Volpe M. Pathogenesis of chronic cardiorenal syndrome: is there a role for oxidative stress? Int J Mol Sci. 2013; 14:23011-23032.
  57. Sumida M, Doi K, Ogasawara E, Yamashita T, Hamasaki Y, Kariya T, Takimoto E, Yahagi N, Nangaku M, Noiri E. Regulation of mitochondrial dynamics by dynamin-related protein-1 in acute cardiorenal syndrome. J Am Soc Nephrol. 2015; 26:2378-2387.
  58. Youssef MI, Mahmoud AA, Abdelghany RH. A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats. Biochem Pharmacol. 2015; 96:20-29.
  59. Trentin-Sonoda M, da Silva RC, Kmit FV, Abrahão MV, Monnerat Cahli G, Brasil GV, Muzi-Filho H, Silva PA, Tovar-Moll FF, Vieyra A, Medei E, Carneiro-Ramos MS. Knockout of Toll-Like Receptors 2 and 4 Prevents Renal Ischemia-Reperfusion-Induced Cardiac Hypertrophy in Mice. PLoS One. 2015;10: Article ID e0139350,1-21.
  60. Junho CVC, González-Lafuente L, Navarro-García J A, Rodríguez-Sánchez E, Carneiro-Ramos MS, Ruiz-Hurtado G. Unilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandling. International journal of molecular sciences. 2022; 23: Article ID 2266,1-15.
  61. Cirino-Silva R, Kmit FV, Trentin-Sonoda M, Nakama KK, Panico K, Alvim JM, Dreyer TR, Martinho-Silva H, Carneiro-Ramos MS. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization. JRSM Cardiovasc Dis. 2017; 6: Article ID 2048004016689440,1-10
  62. Dorn GW 2nd, Kitsis RN. The mitochondrial dynamism-mitophagy-cell death interactome: multiple roles performed by members of a mitochondrial molecular ensemble. Circ Res. 2015; 116:167-182.
  63. Bueno M, Lai YC, Romero Y, Brands J, St Croix CM, Kamga C, Corey C, Herazo-Maya JD, Sembrat J, Lee JS, Duncan SR, Rojas M, Shiva S, Chu CT, Mora AL. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J Clin Invest. 2015; 125:521- 538.
  64. Zimmermann M, Reichert AS. How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways. Biol Chem. 2017; 399:29-45.
  65. Lee YH, Kim SH, Kang JM, Heo JH, Kim DJ, Park SH, Sung M, Kim J, Oh J, Yang DH, Lee SH, Lee SY. Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy. Am J Physiol Renal Physiol. 2019; 317: F767-F780.
  66. Pugsley HR. Assessing autophagic flux by measuring LC3, p62, and LAMP1 co-localization using multispectral imaging flow cytometry. J Vis Exp. 2017; 125: Article ID 55637,1-13.
  67. Zeng X, Zhang YD, Ma RY, Chen YJ, Xiang XM, Hou DY, Li XH, Huang H, Li T, Duan CY. Activated Drp1 regulates p62-mediated autophagic flux and aggravates inflammation in cerebral ischemia-reperfusion via the ROS-RIP1/RIP3-exosome axis. Mil Med Res. 2022; 9: Article ID 25,1-17.
  68. Ma N, Wei Z, Hu J, Gu W, Ci X. Farrerol Ameliorated Cisplatin-Induced Chronic Kidney Disease Through Mitophagy Induction viaNrf2/PINK1 Pathway. Front Pharmacol. 2021; 12: Article ID 768700,1-15.
  69. Feng Z, Jiang HX, Chen H, Liu YN, Wang Y, Yang RB, Han X, Xia CH, Zhu ZB, Shang H, Wu A, Liu WJ. Adaptive Autophagy Offers Cardiorenal Protection in Rats with Acute Myocardial Infarction. Cardiol Res Pract. 2020; 2020: Article ID 7158975,1-10. 
  70. Qi J, Xue Q, Kuang L, Xie L, Luo R, Nie X. Berberine alleviates cisplatin-induced acute kidney injury by regulating mitophagy via PINK 1/Parkin pathway. Transl Androl Urol. 2020; 9:1712-1724.
  71. Wang S, Zhao Z, Fan Y, Zhang M, Feng X, Lin J, Hu J, Cheng Z, Sun C, Liu T, Xiong Z, Yang Z, Wang H, Sun D. Mst1 inhibits Sirt3 expression and contributes to diabetic cardiomyopathy through inhibiting Parkin-dependent mitophagy. Biochim Biophys Acta Mol Basis Dis. 2019; 1865:1905-1914.
  72. Yu W, Gao B, Li N, Wang J, Qiu C, Zhang G, Liu M, Zhang R, Li C, Ji G, Zhang Y. Sirt3 deficiency exacerbates diabetic cardiac dysfunction: Role of Foxo3A-Parkin-mediated mitophagy. Biochim Biophys Acta Mol Basis Dis. 2017; 1863:1973-1983. 
  73. Peng S, Lu XF, Qi YD, Li J, Xu J, Yuan TY, Wu XY, Ding Y, Li WH, Zhou GQ, Wei Y, Li J, Chen SW, Liu SW. LCZ696 Ameliorates Oxidative Stress and Pressure Overload-Induced Pathological Cardiac Remodeling by Regulating the Sirt3/MnSOD Pathway. Oxid Med Cell Longev. 2020; 2020: Article ID 9815039,1-15.
  74. Shi T, Wang F, Stieren E and Tong Q: SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem.2005: 280: 13560‑13567.
  75. He H, Tao H, Xiong H, Duan SZ, McGowan FX Jr, Mortensen RM, Balschi JA. Rosiglitazone causes cardiotoxicity via peroxisome proliferator-activated receptor γ-independent mitochondrial oxidative stress in mouse hearts. Toxicol Sci. 2014; 138:468-
  76. Kim T, Yang Q. “Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system,” World Journal of Cardiology. 2013; 5: 164–174.
  77. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR, Gius D. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell. 2010; 40:893-904. 
  78. Chen L, Qin Y, Liu B, Gao M, Li A, Li X, Gong G. PGC-1α-Mediated Mitochondrial Quality Control: Molecular Mechanisms and Implications for Heart Failure. Front Cell Dev Biol. 2022; 10: Article ID 871357,1-12. 
  79. Buys-Gonçalves GF, Sampaio FJB, Silva MEM, Pereira-Sampaio MA, De Souza DB. Histomorphometric evaluation of the rat kidney submitted to warm ischemia and the protective effect of resveratrol. American journal of surgery. 2020; 220: 1119–1123.
  80. Yang M, Xi N, Gao M, Yu Y. Sitagliptin mitigates hypoxia/reoxygenation (H/R)-induced injury in cardiomyocytes by mediating sirtuin 3 (SIRT3) and autophagy. Bioengineered. 2022; 13:13162-13173. 
  81. Prud'homme M, Coutrot M, Michel T, Boutin L, Genest M, Poirier F, Launay JM, Kane B, Kinugasa S, Prakoura N, Vandermeersch S, Cohen-Solal A, Delcayre C, Samuel JL, Mehta R, Gayat E, Mebazaa A, Chadjichristos CE, Legrand M. Acute Kidney Injury Induces Remote Cardiac Damage and Dysfunction Through the Galectin-3 Pathway. JACC Basic Transl Sci. 2019; 4:717-732.
  82. Florens N, Kasam RK, Rudman-Melnick V, Lin SC, Prasad V, Molkentin JD. Interleukin-33 Mediates Cardiomyopathy After Acute Kidney Injury by Signaling to Cardiomyocytes. Circulation. 2023; 147:746-758.
  83. Han WK, Alinani A, Wu CL, Michaelson D, Loda M, McGovern FJ, Thadhani R, Bonventre JV. Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol. 2005; 16:1126-
  84. Yanagita M. Inhibitors/antagonists of TGF-beta system in kidney fibrosis. Nephrol Dial Transpl. 2012; 27:3686–3691
  85. Lamberti Y, Perez Vidakovics ML, van der Pol LW, Rodríguez ME. Cholesterol-rich domains are involved in Bordetella pertussis phagocytosis and intracellular survival in neutrophils. Microb Pathog. 2008; 44:501-                                                                    
  86. Sun Y, Zhang JQ, Zhang J, Lamparter S. Cardiac remodeling by fibrous tissue after infarction in rats. J Lab Clin Med. 2000; 135:316- 323.
  87. Wynn TA. Cellular and molecular mechanisms of fibrosis.J Pathol. 2008; 214: 199–210
  88. Talman V, Ruskoaho H. Cardiac fibrosis in myocardial infarction-from repair and remodeling to regeneration. Cell Tissue Res. 2016; 365:563-581.
  89. Hu J, Liu T, Fu F, Cui Z, Lai Q, Zhang Y, Yu B, Liu F, Kou J, Li F. Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy. J Transl Med. 2022; 20: Article ID 447,1-21.
  90. Bjørkøy G, Lamark T, Pankiv S, Øvervatn A, Brech A, Johansen T. Monitoring Autophagic Degradation of p62/SQSTM1. Methods Enzymol. 2009; 452: 181-197.          
  91. Kang R, Zeh HJ, Lotze MT, Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011; 18:571- 580.
  92. Zhang J, Xiang H, Liu J, Chen Y, He RR, Liu B. Mitochondrial Sirtuin 3: new emerging biological function and therapeutic target. Theranostics. 2020; 10:8315– 8342.
  93. Singh CK, Chhabra G, Ndiaye MA, Garcia-Peterson LM, Mack NJ, Ahmad N. The Role of Sirtuins in Antioxidant and Redox Signaling. Antioxid Redox Signal. 2018; 28:643-661.
  94. Gao YM, Feng ST, Wen Y, Tang TT, Wang B, Liu BC. Cardiorenal protection of SGLT2 inhibitors-Perspectives from metabolic reprogramming. EBioMedicine. 2022; 83: Article ID 104215,1-15.
  95. Salvatore T, Galiero R, Caturano A, Rinaldi L, Di Martino A, Albanese G, Di Salvo J, Epifani R, Marfella R, Docimo G, Lettieri M, Sardu C, Sasso FC. An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors. Int J Mol Sci. 2022; 23: Article ID 3651,1-44.
  96. Yang CC, Chen YT, Wallace CG, Chen KH, Cheng BC, Sung PH, Li YC, Ko SF, Chang HW, Yip HK. Early administration of empagliflozin preserved heart function in cardiorenal syndrome in rat. Biomed Pharmacother. 2019; 109:658-670.
  97. Lu Q, Liu J, Li X, Sun X, Zhang J, Ren D, Tong N, Li J. Empagliflozin attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway. Mol Cell Endocrinol. 2020; 501: Article ID 110642,1-11.
  98. Tan Y, Yu K, Liang L, Liu Y, Song F, Ge Q, Fang X, Yu T, Huang Z, Jiang L, Wang P. Sodium-Glucose Co-Transporter 2 Inhibition with Empagliflozin Improves Cardiac Function After Cardiac Arrest in Rats by Enhancing Mitochondrial Energy Metabolism. Front Pharmacol. 2021; 12: Article ID 758080,1-12.
  99. Zhao C, Chen Z, Xu X, An X, Duan S, Huang Z, Zhang C, Wu L, Zhang B, Zhang A, Xing C, Yuan Y. Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury. Exp Cell Res. 2017; 350:390-397.
  100. Ala M, Khoshdel MRF, Dehpour AR. Empagliflozin Enhances Autophagy, Mitochondrial Biogenesis, and Antioxidant Defense and Ameliorates Renal Ischemia/Reperfusion in Nondiabetic Rats. Oxid Med Cell Longev. 2022; 2022: Article ID 1197061,1-9.
  101. Wang CY, Chen CC, Lin MH, Su HT, Ho MY, Yeh JK, Tsai ML, Hsieh IC, Wen MS. TLR9 Binding to Beclin 1 and Mitochondrial SIRT3 by a Sodium-Glucose Co-Transporter 2 Inhibitor Protects the Heart from Doxorubicin Toxicity. Biology (Basel). 2020; 9: Article ID 369,1-22.
  102. Oshima H, Miki T, Kuno A, Mizuno M, Sato T, Tanno M, Yano T, Nakata K, Kimura Y, Abe K, Ohwada W, Miura T. Empagliflozin, an SGLT2 Inhibitor, Reduced the Mortality Rate after Acute Myocardial Infarction with Modification of Cardiac Metabolomes and Antioxidants in Diabetic Rats. J Pharmacol Exp Ther. 2019; 368:524-534.
  103. Tseng AH, Wu LH, Shieh SS, and Wang DL. SIRT3 interactions with FOXO3 acetylation, phosphorylation and ubiquitinylation mediate endothelial cell responses to hypoxia. Biochem J. 2014; 464:157–168.
Statistics
Article View: 206
PDF Download: 172