AKAP1 in Renal Patients with AHF to Reduce Ferroptosis of Cardiomyocyte

Authors

  • Yifeng Fang Department of Emergency, The First People's Hospital of Yongkang, 321390 Yongkang, Zhejiang, China
  • Junpeng Xu Department of Emergency, The First People's Hospital of Yongkang, 321390 Yongkang, Zhejiang, China
  • Ruofei Huang Department of Endocrine, The First People's Hospital of Yongkang, 321390 Yongkang, Zhejiang, China

DOI:

https://doi.org/10.59958/hsf.5717

Keywords:

AKAP1, AHF, chronic kidney disease, NDUFS, ferroptosis

Abstract

Background: This study mainly investigated the mechanism and effects of AKAP1 in renal patients with acute heart failure (AHF). Methods: Patients with renal patients with AHF and normal volunteers were collected. The left anterior descending arteries (LAD) of mice were ligated to induce myocardial infarction. Results: AKAP1 messenger RNA (mRNA) expression was found to be down-regulated in renal patients with AHF. The serum levels of AKAP1 mRNA expression were negatively correlated with collagen I/III in patients. AKAP1 mRNA and protein expression in the heart tissue of mice with AHF were also found to be down-regulated in a time-dependent manner. Short hairpin (Sh)-AKAP1 promotes AHF in a mouse model. AKAP1 up-regulation reduces reactive oxygen species (ROS)-induced oxidative stress in an In Vitro model. AKAP1 up-regulation also reduces ROS-induced lipid peroxidation ferroptosis in an In Vitro model. AKAP1 induces NDUFS1 expression to increase GPX4 activity levels. AKAP1 protein interlinked with the NDUFS1 protein. Up-regulation of the AKAP1 gene reduced NDUFS1 ubiquitination, while down-regulation of the AKAP1 gene increased NDUFS1 ubiquitination in a model. In vivo imaging showed that the sh-AKAP1 virus reduced NDUFS1 expression in the heart of a mouse model. Conclusions: AKAP1 reduced ROS-induced lipid peroxidation ferroptosis through the inhibition of ubiquitination of NDUFS by mitochondrial damage in model of renal patients with AHF, suggest a novel target for AHF treatment.

References

Chuzi S, Tanaka Y, Bavishi A, Bruce M, Van Wagner LB, Wilcox JE, et al. Association Between End-Stage Liver Disease and Incident Heart Failure in an Integrated Health System. Journal of General Internal Medicine. 2023; 38: 2445–2452.

Chertow GM, Correa-Rotter R, Vart P, Jongs N, McMurray JJV, Rossing P, et al. Effects of Dapagliflozin in Chronic Kidney Disease, With and Without Other Cardiovascular Medications: DAPA-CKD Trial. Journal of the American Heart Association. 2023; 12: e028739.

Schulman IH, Chan K, Der JS, Wilkins KJ, Corns HL, Sayer B, et al. Readmission and Mortality After Hospitalization With Acute Kidney Injury. American Journal of Kidney Diseases: the official journal of the National Kidney Foundation 2023; 82: 63–74.e61.

Beldhuis IE, Lam CSP, Testani JM, Voors AA, Van Spall HGC, Ter Maaten JM, et al. Evidence-Based Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Chronic Kidney Disease. Circulation. 2022; 145: 693–712.

Han X, Zhang S, Chen Z, Adhikari BK, Zhang Y, Zhang J, et al. Cardiac biomarkers of heart failure in chronic kidney disease. Clinica Chimica Acta; International Journal of Clinical Chemistry. 2020; 510: 298–310.

Filippatos G, Pitt B, Agarwal R, Farmakis D, Ruilope LM, Rossing P, et al. Finerenone in patients with chronic kidney disease and type 2 diabetes with and without heart failure: a prespecified subgroup analysis of the FIDELIO-DKD trial. European Journal of Heart Failure. 2022; 24: 996–1005.

Haynes R, Zhu D, Judge PK, Herrington WG, Kalra PA, Baigent C. Chronic kidney disease, heart failure and neprilysin inhibition. Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2020; 35: 558–564.

Komai K, Kawasaki NK, Higa JK, Matsui T. The Role of Ferroptosis in Adverse Left Ventricular Remodeling Following Acute Myocardial Infarction. Cells. 2022; 11: 1399.

Mancardi D, Mezzanotte M, Arrigo E, Barinotti A, Roetto A. Iron Overload, Oxidative Stress, and Ferroptosis in the Failing Heart and Liver. Antioxidants (Basel, Switzerland). 2021; 10: 1864.

Miyamoto HD, Ikeda M, Ide T, Tadokoro T, Furusawa S, Abe K, et al. Iron Overload via Heme Degradation in the Endoplasmic Reticulum Triggers Ferroptosis in Myocardial Ischemia-Reperfusion Injury. JACC. Basic to Translational Science. 2022; 7: 800–819.

Ji L, Zhao Y, He L, Zhao J, Gao T, Liu F, et al. AKAP1 Deficiency Attenuates Diet-Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes. Advanced Science (Weinheim, Baden-Wurttemberg, Germany). 2021; 8: 2002794.

Marin W. A-kinase anchoring protein 1 (AKAP1) and its role in some cardiovascular diseases. Journal of Molecular and Cellular Cardiology. 2020; 138: 99–109.

Qi B, He L, Zhao Y, Zhang L, He Y, Li J, et al. Akap1 deficiency exacerbates diabetic cardiomyopathy in mice by NDUFS1-mediated mitochondrial dysfunction and apoptosis. Diabetologia. 2020; 63: 1072–1087.

Schiattarella GG, Cattaneo F, Carrizzo A, Paolillo R, Boccella N, Ambrosio M, et al. Akap1 Regulates Vascular Function and Endothelial Cells Behavior. Hypertension (Dallas, Tex.: 1979). 2018; 71: 507–517.

Feng J, Chen Z, Ma Y, Yang X, Zhu Z, Zhang Z, et al. AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease. International Journal of Biological Sciences. 2022; 18: 4026–4042.

Flippo KH, Gnanasekaran A, Perkins GA, Ajmal A, Merrill RA, Dickey AS, et al. AKAP1 Protects from Cerebral Ischemic Stroke by Inhibiting Drp1-Dependent Mitochondrial Fission. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience. 2018; 38: 8233–8242.

Zhou Q, Pan LL, Xue R, Ni G, Duan Y, Bai Y, et al. The anti-microbial peptide LL-37/CRAMP levels are associated with acute heart failure and can attenuate cardiac dysfunction in multiple preclinical models of heart failure. Theranostics. 2020; 10: 6167–6181.

Qiao L, Hu S, Liu S, Zhang H, Ma H, Huang K, et al. microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential. The Journal of Clinical Investigation. 2019; 129: 2237–2250.

Qiu Z, He Y, Ming H, Lei S, Leng Y, Xia ZY. Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes. Journal of Diabetes Research. 2019; 2019: 8151836.

Pu Z, Han C, Zhang W, Xu M, Wu Z, Liu Y, et al. Systematic understanding of the mechanism and effects of Arctigenin attenuates inflammation in dextran sulfate sodium-induced acute colitis through suppression of NLRP3 inflammasome by SIRT1. American Journal of Translational Research. 2019; 11: 3992–4009.

Zhang W, Wang W, Xu M, Xie H, Pu Z. GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis. Aging. 2021; 13: 22588–22610.

Pu Z, Shen C, Zhang W, Xie H, Wang W. Avenanthramide C from Oats Protects Pyroptosis through Dependent ROS-Induced Mitochondrial Damage by PI3K Ubiquitination and Phosphorylation in Pediatric Pneumonia. Journal of Agricultural and Food Chemistry. 2022; 70: 2339–2353.

Lunney M, Ruospo M, Natale P, Quinn RR, Ronksley PE, Konstantinidis I, et al. Pharmacological interventions for heart failure in people with chronic kidney disease. The Cochrane Database of Systematic Reviews. 2020; 2: CD012466.

Iso T, Matsue Y, Mizukami A, Tokano T, Isoda K, Suwa S, et al. Daprodustat for anaemia in patients with heart failure and chronic kidney disease: A randomized controlled study. ESC Heart Failure. 2022; 9: 4291–4297.

Ameri P, De Marzo V, Zoccai GB, Tricarico L, Correale M, Brunetti ND, et al. Efficacy of new medical therapies in patients with heart failure, reduced ejection fraction, and chronic kidney disease already receiving neurohormonal inhibitors: a network meta-analysis. European Heart Journal. Cardiovascular Pharmacotherapy. 2022; 8: 768–776.

Wang X, Li Q, Sui B, Xu M, Pu Z, Qiu T. Schisandrin A from Schisandra chinensis Attenuates Ferroptosis and NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy through Mitochondrial Damage by AdipoR1 Ubiquitination. Oxidative Medicine and Cellular Longevity. 2022; 2022: 5411462.

Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, et al. Ferroptosis: past, present and future. Cell Death & Disease. 2020; 11: 88.

Liu MY, Li HM, Wang XY, Xia R, Li X, Ma YJ, et al. TIGAR drives colorectal cancer ferroptosis resistance through ROS/AMPK/SCD1 pathway. Free Radical Biology & Medicine. 2022; 182: 219–231.

Niu B, Liao K, Zhou Y, Wen T, Quan G, Pan X, et al. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy. Biomaterials. 2021; 277: 121110.

Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021; 17: 2054–2081.

Cui X, Tian Y, Zhao Y, Gao H, Yao D, Liu L, et al. miR-199b-5p-AKAP1-DRP1 Pathway Plays a Key Role in ox-LDL-induced Mitochondrial Fission and Endothelial Apoptosis. Current Pharmaceutical Biotechnology. 2022; 23: 1612–1622.

Wan S, Maitiabula G, Wang P, Zhang Y, Gao X, Zhang L, et al. Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress. The Journal of Nutritional Biochemistry. 2023; 112: 109221.

Qi B, Song L, Hu L, Guo D, Ren G, Peng T, et al. Cardiac-specific overexpression of Ndufs1 ameliorates cardiac dysfunction after myocardial infarction by alleviating mitochondrial dysfunction and apoptosis. Experimental & Molecular Medicine. 2022; 54: 946–960.

Wiebringhaus R, Pecoraro M, Neubauer HA, Trachtová K, Trimmel B, Wieselberg M, et al. Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer. Cancers. 2021; 13: 6036.

Published

2024-01-14

How to Cite

Fang, Y., Xu, J. ., & Huang, R. . (2024). AKAP1 in Renal Patients with AHF to Reduce Ferroptosis of Cardiomyocyte. The Heart Surgery Forum, 27(1), E028-E037. https://doi.org/10.59958/hsf.5717

Issue

Section

Article