Correlation analysis of serum PDK4, NLRP3, and PTEN levels in myocardial injury with sepsis

Serum PDK4, NLRP3, and PTEN levels in myocardial injury with sepsis

  • Zebin Fang HaiNing People’s Hospital
  • Xiaoxia Li HaiNing People’s Hospital
  • Zhenfei Ou HaiNing People’s Hospital
  • Jimu Wang Jiangsu Provincial People's Hospital
  • Keji Lin Jiangsu Provincial People's Hospital
  • Shujia Ye HaiNing People’s Hospital
Keywords: Sepsis-induced myocardial injury, Pyruvate dehydrogenase kinase 4 (PDK4), Nod-like receptor protein 3 (NLRP3), Protein homolog, Prognostic correlation

Abstract


Objective: To explore the correlations between the levels of serum pyruvate dehydrogenase kinase 4 (PDK4), NOD-like receptor protein 3 (NLRP3), and phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and myocardial injury indicators as well as prognosis in patients with sepsis.

Methods: A total of 355 patients who were first diagnosed with sepsis and admitted to our hospital from September 2022 to September 2024 were included. Depending on whether they suffered myocardial damage, the patients were split into two groups: the septic myocardial injury (SIMI) group (225 patients) and the simple sepsis group (130 patients). According to their survival outcomes after 28 days of treatment, the patients were divided into two groups: the death group (56 patients) and the survival group (169 patients). The levels of serum PDK4, NLRP3 and PTEN were detected via real-time fluorescence quantitative PCR (qRT‒PCR). An automatic biochemical analyzer was used to measure the levels of myoglobin (Mb), cardiac troponin I (cTnI), creatine kinase isoenzyme (CK-MB), and heart-type fatty acid binding protein (H-FABP). The Pearson correlation coefficient method was used to analyze the relationships between serum PDK4, NLRP3, and PTEN levels and myocardial injury indicators in SIMI patients. Cox regression analysis was employed to examine the variables affecting SIMI patients' prognoses.

Results: The levels of serum PDK4, NLRP3, PTEN, CK-MB, cTnI, Mb and H-FABP in the SIMI group were significantly greater than those in the simple sepsis group (P<0.05). The levels of serum PDK4, NLRP3 and PTEN in patients with sepsis were positively correlated with the myocardial injury indicators CK-MB, cTnI, Mb and H-FABP (P<0.05). The APACHE II score, SOFA score, cTnI, and the levels of serum PDK4, NLRP3 and PTEN in the prognosis death group of SIMI patients were greater than those in the survival group (P<0.05). Independent risk variables that impact the prognosis of patients with SIMI include the APACHE II score, SOFA score, cTnI, PDK4, NLRP3, and PTEN (P<0.05).

Conclusion: Serum PDK4, NLRP3 and PTEN, which are independent risk factors affecting the prognosis of SIMI patients, are highly expressed in SIMI patients.

References

1.Zhou B, Zhang J, Chen Y, Liu Y, Tang X, Xia P, Yu P, Yu S. Puerarin protects against sepsis-induced myocardial injury through AMPK-mediated ferroptosis signaling. Aging (Albany NY). 2022 Apr 28;14(8):3617-3632. doi: 10.18632/aging.204033. Epub 2022 Apr 28. PMID: 35482440; PMCID: PMC9085223.
2.Liu C, Zou Q, Tang H, Liu J, Zhang S, Fan C, Zhang J, Liu R, Liu Y, Liu R, Zhao Y, Wu Q, Qi Z, Shen Y. Melanin nanoparticles alleviate sepsis-induced myocardial injury by suppressing ferroptosis and inflammation. Bioact Mater. 2022 Dec 27;24:313-321. doi: 10.1016/j.bioactmat.2022.12.026. PMID: 36632502; PMCID: PMC9813528.
3.Dong Y, Wei S, Liu Y, Ji X, Yin X, Wu Z, Wu S, Wang B, Wei S, Chen Y. Aspirin is associated with improved outcomes in patients with sepsis-induced myocardial injury: An analysis of the MIMIC-IV database. J Clin Anesth. 2024 Dec;99:111597. doi: 10.1016/j.jclinane.2024.111597. Epub 2024 Sep 7. PMID: 39245010.
4.Xiao Y, Yu Y, Hu L, Yang Y, Yuan Y, Zhang W, Luo J, Yu L. Matrine Alleviates Sepsis-Induced Myocardial Injury by Inhibiting Ferroptosis and Apoptosis. Inflammation. 2023 Oct;46(5):1684-1696. doi: 10.1007/s10753-023-01833-2. Epub 2023 May 23. Erratum in: Inflammation. 2024 Aug;47(4):1545. doi: 10.1007/s10753-024-01976-w. PMID: 37219694.
5.Bi CF, Liu J, Yang LS, Zhang JF. Research Progress on the Mechanism of Sepsis Induced Myocardial Injury. J Inflamm Res. 2022 Jul 26;15:4275-4290. doi: 10.2147/JIR.S374117. PMID: 35923903; PMCID: PMC9342248.
6.Fang D, Li Y, He B, Gu D, Zhang M, Guo J, Ren H, Li X, Zhang Z, Tang M, Li X, Yang D, Xu C, Hu Y, Wang H, Jose PA, Han Y, Zeng C. Gastrin attenuates sepsis-induced myocardial dysfunction by downregulation of TLR4 expression in macrophages. Acta Pharm Sin B. 2023 Sep;13(9):3756-3769. doi: 10.1016/j.apsb.2023.06.012. Epub 2023 Jun 23. PMID: 37719375; PMCID: PMC10502292.
7.She H, Tan L, Du Y, Zhou Y, Guo N, Zhang J, Du Y, Wang Y, Wu Z, Ma C, Li Q, Mao Q, Hu Y, Liu L, Li T. VDAC2 malonylation participates in sepsis-induced myocardial dysfunction via mitochondrial-related ferroptosis. Int J Biol Sci. 2023 Jun 14;19(10):3143-3158. doi: 10.7150/ijbs.84613. PMID: 37416771; PMCID: PMC10321281.
8.Zhen G, Liang W, Jia H, Zheng X. Melatonin relieves sepsis-induced myocardial injury by regulating JAK2/STAT3 signaling pathway. Minerva Med. 2022 Dec;113(6):983-989. doi: 10.23736/S0026-4806.20.06626-4. Epub 2020 Jul 17. PMID: 32683850.
9.Pei H, Qu J, Chen J, Zhao G, Lu Z. S100A9 as a Key Myocardial Injury Factor Interacting with ATP5 Exacerbates Mitochondrial Dysfunction and Oxidative Stress in Sepsis-Induced Cardiomyopathy. J Inflamm Res. 2024 Jul 9;17:4483-4503. doi: 10.2147/JIR.S457340. Erratum in: J Inflamm Res. 2024 Jul 23;17:4921-4922. doi: 10.2147/JIR.S487243. PMID: 39006491; PMCID: PMC11246037.
10.Wang X, Xie D, Dai H, Ye J, Liu Y, Fei A. Clemastine protects against sepsis-induced myocardial injury in vivo and in vitro. Bioengineered. 2022 Mar;13(3):7134-7146. doi: 10.1080/21655979.2022.2047256. PMID: 35274595; PMCID: PMC9208445.
11.Zeng N, Jian Z, Zhu W, Xu J, Fan Y, Xiao F. KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced inflammation and apoptosis. Int J Exp Pathol. 2023 Feb;104(1):23-32. doi: 10.1111/iep.12459. Epub 2022 Dec 30. PMID: 36583453; PMCID: PMC9845607.
12.Zhang R, Niu Z, Liu J, Dang X, Feng H, Sun J, Pan L, Peng Z. LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1. J Cell Mol Med. 2022 Jul;26(13):3648-3658. doi: 10.1111/jcmm.17358. Epub 2022 Jun 9. PMID: 35678255; PMCID: PMC9258699.
13.Wu L, Zheng Y, Liu J, Luo R, Wu D, Xu P, Wu D, Li X. Comprehensive evaluation of the efficacy and safety of LPV/r drugs in the treatment of SARS and MERS to provide potential treatment options for COVID-19. Aging (Albany NY). 2021 Apr 20;13(8):10833-10852. doi: 10.18632/aging.202860. Epub 2021 Apr 20. PMID: 33879634; PMCID: PMC8109137.
14.Fu W, Fang X, Wu L, Hu W, Yang T. Neogambogic acid relieves myocardial injury induced by sepsis viap38 MAPK/NF-κB pathway. Korean J Physiol Pharmacol. 2022 Nov 1;26(6):511-518. doi: 10.4196/kjpp.2022.26.6.511. PMID: 36302625; PMCID: PMC9614397.
15.Yang H, Jiang Z, Feng L, Wang C, Xu H, Wu X, Lin C, Zeng K. Nppb contributes to Sepsis-Induced myocardial injury by regulating Senescence-Related genes. Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113461. doi: 10.1016/j.intimp.2024.113461. Epub 2024 Oct 23. PMID: 39447413.
16.Yang W, Cao Y, Li J, Zhang X, Liu X, Tian Y, Shan L, Yang Y. Pathogenesis and treatment strategies of sepsis-induced myocardial injury: modern and traditional medical perspectives. Int J Biol Sci. 2025 May 15;21(8):3478-3504. doi: 10.7150/ijbs.111288. PMID: 40520010; PMCID: PMC12160516.
17.Wu L, Zhong Y, Wu D, Xu P, Ruan X, Yan J, Liu J, Li X. Immunomodulatory Factor TIM3 of Cytolytic Active Genes Affected the Survival and Prognosis of Lung Adenocarcinoma Patients by Multi-Omics Analysis. Biomedicines. 2022 Sep 10;10(9):2248. doi: 10.3390/biomedicines10092248. PMID: 36140350; PMCID: PMC9496572.
18.Cheng L, Liu D, Gao S. PPARA ameliorates sepsis-induced myocardial injury by promoting macrophage M2 polarization by interacting with DUSP1. Regen Ther. 2024 May 18;26:33-41. doi: 10.1016/j.reth.2024.04.017. PMID: 38798745; PMCID: PMC11126881.
19.Huang G, Zhao X, Bai Y, Liu J, Li W, Wu Y. Regulation of mitochondrial autophagy by lncRNA MALAT1 in sepsis-induced myocardial injury. Eur J Med Res. 2024 Nov 1;29(1):524. doi: 10.1186/s40001-024-02098-7. PMID: 39487520; PMCID: PMC11531147.
20.Jin Y, Fleishman JS, Ma Y, Jing X, Guo Q, Shang W, Wang H. NLRP3 Inflammasome Targeting Offers a Novel Therapeutic Paradigm for Sepsis-Induced Myocardial Injury. Drug Des Devel Ther. 2025 Feb 14;19:1025-1041. doi: 10.2147/DDDT.S506537. PMID: 39967903; PMCID: PMC11834678.
21.Wu L, Liu Q, Ruan X, Luan X, Zhong Y, Liu J, Yan J, Li X. Multiple Omics Analysis of the Role of RBM10 Gene Instability in Immune Regulation and Drug Sensitivity in Patients with Lung Adenocarcinoma (LUAD). Biomedicines. 2023 Jun 29;11(7):1861. doi: 10.3390/biomedicines11071861. PMID: 37509501; PMCID: PMC10377220.
22.Zhang L, Li B, Li W, Jiang J, Chen W, Yang H, Pan D. miR-107 Attenuates Sepsis-Induced Myocardial Injury by Targeting PTEN and Activating the PI3K/AKT Signaling Pathway. Cells Tissues Organs. 2023;212(6):523-534. doi: 10.1159/000525476. Epub 2022 Jun 17. PMID: 35717938.
23.Liu W, Guo X, Jin L, Hong T, Zhang Q, Su F, Shen Y, Li S, He B. Lipocalin-2 participates in sepsis-induced myocardial injury by mediating lipid accumulation and mitochondrial dysfunction. Front Cardiovasc Med. 2022 Nov 7;9:1009726. doi: 10.3389/fcvm.2022.1009726. PMID: 36419491; PMCID: PMC9676239.
24.Wu L, Zheng Y, Ruan X, Wu D, Xu P, Liu J, Wu D, Li X. Long-chain noncoding ribonucleic acids affect the survival and prognosis of patients with esophageal adenocarcinoma through the autophagy pathway: construction of a prognostic model. Anticancer Drugs. 2022 Jan 1;33(1):e590-e603. doi: 10.1097/CAD.0000000000001189. PMID: 34338240; PMCID: PMC8670349.
25.Li X, Sun H, Zhang L, Liang H, Zhang B, Yang J, Peng X, Sun J, Zhou Y, Zhai M, Jiang L, Zhu H, Duan W. GDF15 attenuates sepsis-induced myocardial dysfunction by inhibiting cardiomyocytes ferroptosis via the SOCS1/GPX4 signaling pathway. Eur J Pharmacol. 2024 Nov 5;982:176894. doi: 10.1016/j.ejphar.2024.176894. Epub 2024 Aug 13. PMID: 39147013.
26.Li J, Jiang R, Hou Y, Lin A. Mesenchymal stem cells-derived exosomes prevent sepsis-induced myocardial injury by a CircRTN4/miR-497-5p/MG53 pathway. Biochem Biophys Res Commun. 2022 Aug 27;618:133-140. doi: 10.1016/j.bbrc.2022.05.094. Epub 2022 Jun 3. PMID: 35724457.
27.Xie Y, Zhang J, Jin W, Tian R, Wang R. [Corrigendum] Role of Thrombospondin1 in sepsisinduced myocardial injury. Mol Med Rep. 2023 Jun;27(6):113. doi: 10.3892/mmr.2023.13000. Epub 2023 Apr 21. Erratum for: Mol Med Rep. 2021 Dec;24(6):869. doi: 10.3892/mmr.2021.12509. PMID: 37083065; PMCID: PMC10170490.
28.Zhao L, Zhao H, Sun M, Chen M, Wu X, Deng C, Yang W, Tian Y, Wang Q, Liang Z, Xu X, Yang Y. Kudzu Celery Decoction Exerts Protection against Sepsis-Induced Myocardial Injury. Oxid Med Cell Longev. 2022 May 4;2022:2886932. doi: 10.1155/2022/2886932. PMID: 35571240; PMCID: PMC9095356.
29.Wu L, Zhong Y, Yu X, Wu D, Xu P, Lv L, Ruan X, Liu Q, Feng Y, Liu J, Li X. Selective poly adenylation predicts the efficacy of immunotherapy in patients with lung adenocarcinoma by multiple omics research. Anticancer Drugs. 2022 Oct 1;33(9):943-959. doi: 10.1097/CAD.0000000000001319. Epub 2022 Aug 9. PMID: 35946526; PMCID: PMC9481295.
30.Guo P, Xue L, Tao F, Yang K, Gao Y, Pei C. Prognostic analysis of sepsis-induced myocardial injury patients using propensity score matching and doubly robust analysis with machine learning-based risk prediction model development. Front Med (Lausanne). 2025 Feb 19;12:1555103. doi: 10.3389/fmed.2025.1555103. PMID: 40046920; PMCID: PMC11880261.
Published
2025/10/27
Section
Original paper