Skip to main content
SpringerLink
Log in

Exploring the Diagnostic Utility of Serum Cofilin-1 and 2 Levels in Patients with Acute Coronary Syndrome: A Case–Control Pilot Study

  • ORIGINAL RESEARCH ARTICLE
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Acute coronary syndrome (ACS) is caused by decreased blood flow to the heart muscle after plaque rupture and thrombus formation, leading to ischemia and infarction. Cofilins are the proteins involved in actin dynamics by severing and dissociating actin filaments. Abnormal cofilins are associated with myopathies, idiopathic dilated cardiomyopathies, etc. As ACS prevalence is increasing and there is a need to find specific biomarkers for ACS diagnosis, the study aimed to assess the diagnostic utility of serum cofilin-1 (CFL-1) and 2 (CFL-2) levels in ACS patients. Forty-five ACS patients as cases and 45 healthy participants as controls were recruited in a case–control pilot study. Collected blood was used to measure serum CFL-1, CFL-2 and heart-type fatty acid-binding protein (H-FABP, a marker of myocardial infarction) levels. Serum CFL-2 levels were significantly lower in cases compared to controls (2.93 [1.95–3.32] vs. 4.35 [3.4–6.61], p < 0.05). No significant difference was observed in serum CFL-1 levels between groups. Serum CFL-2 levels were negatively associated with creatine kinase–total, creatine kinase–MB, creatine kinase–MB relative index, troponin-T, and H-FABP (p < 0.05). Binary logistic regression showed lower CFL-2 levels were associated with a 2.45-fold increased ACS risk. ROC analysis showed no advantage of serum CFL-2 levels over serum H-FABP levels for ACS diagnosis (AUC: 0.120 Vs 0.710, p > 0.05). In conclusion, serum CFL-1 and 2 levels may not have greater significance in ACS diagnosis than traditional cardiac biomarkers. However, further cohort studies with a larger sample size must confirm the study’s findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982–3021. https://doi.org/10.1016/j.jacc.2020.11.010.

  2. Deora S, Kumar T, Ramalingam R, Nanjappa MC. Demographic and angiographic profile in premature cases of acute coronary syndrome: analysis of 820 young patients from South India. Cardiovasc Diagn Ther. 2016;6(3):193–8. https://doi.org/10.21037/cdt.2016.03.05.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Bhatt DL, Lopes RD, Harrington RA. Diagnosis and treatment of acute coronary syndromes: a review. JAMA. 2022;327(7):662–75. https://doi.org/10.1001/jama.2022.0358.

    Article  PubMed  Google Scholar 

  4. Wang XY, Zhang F, Zhang C, Zheng LR, Yang J. The biomarkers for acute myocardial infarction and heart failure. Biomed Res Int. 2020;2020:2018035. https://doi.org/10.1155/2020/2018035.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Abe T, Samuel I, Eferoro E, Samuel AO, Monday IT, Olunu E, et al. The diagnostic challenges associated with type 2 myocardial infarction. Int J Appl Basic Med Res. 2021;11(3):131–8. https://doi.org/10.4103/ijabmr.IJABMR_210_20.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Xu S, Jiang J, Zhang Y, Chen T, Zhu M, Fang C, et al. Discovery of potential plasma protein biomarkers for acute myocardial infarction via proteomics. J Thorac Dis. 2019;11(9):3962–72. https://doi.org/10.21037/jtd.2019.08.100.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Wu Y, Pan N, An Y, Xu M, Tan L, Zhang L. Diagnostic and prognostic biomarkers for myocardial infarction. Front Cardiovasc Med. 2021;7: 617277. https://doi.org/10.3389/fcvm.2020.617277.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Tanaka K, Takeda S, Mitsuoka K, Oda T, Kimura-Sakiyama C, Maéda Y, et al. Structural basis for cofilin binding and actin filament disassembly. Nat Commun. 2018;9(1):1860. https://doi.org/10.1038/s41467-018-04290-w.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  9. Maciver SK, Hussey PJ. The ADF/cofilin family: actin-remodeling proteins. Genome Biol. 2002;3(5):3007.

    Article  Google Scholar 

  10. Ehler E. Actin-associated proteins and cardiomyopathy-the “unknown” beyond troponin and tropomyosin. Biophys Rev. 2018;10(4):1121–8. https://doi.org/10.1007/s12551-018-0428-1.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Kanellos G, Zhou J, Patel H, Radgway RA, Huels D, Gurniak CB, et al. ADF and cofilin1 control actin stress fibers, nuclear integrity, and cell survival. Cell Rep. 2015;13(9):1949–64. https://doi.org/10.1016/j.celrep.2015.10.056.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Blanchoin L, Boujemaa-Paterski R, Sykes C, Plastino J. Actine dynamics, architecture, and mechanics in cell motility. Physiol Rev. 2014;94(1):235–63. https://doi.org/10.1152/physrev.00018.2013.

    Article  CAS  PubMed  Google Scholar 

  13. Kremneva E, Makkonen MH, Skwarek-Maruszewska A, Gateva G, Michelot A, Dominguez R, et al. Cofilin-2 controls actin filament length in muscle sarcomeres. Dev cell. 2014;31(2):215–26. https://doi.org/10.1016/j.devcel.2014.09.002.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Mohri K, Suzuki-Toyota F, Obinata T, Sato N. Chimeric mice with deletion of Cfl2 that encodes muscle-type cofilin (MCF or Cofilin-2) results in defects of striated muscles, both skeletal and cardiac muscles. Zoolog Sci. 2019;36(2):112–9. https://doi.org/10.2108/zs180151.

    Article  CAS  PubMed  Google Scholar 

  15. Subramanian K, Gianni D, Balla C, Assenza GE, Joshi M, Semigran MJ, et al. Cofilin-2 phosphorylation and sequestration in myocardial aggregates: novel pathogenetic mechanisms for idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1199–214. https://doi.org/10.1016/j.jacc.2015.01.031.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Chatzifrangkeskou M, Yadin D, Marais T, Chardonnet S, Cohen-Tannoudji M, Mougenot N, et al. Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet. 2018;27(17):3060–78. https://doi.org/10.1093/hmg/ddy215.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Nguyen K, Chau VQ, Mauro AG, Durrant D, Toldo S, Abbate A, et al. Hydrogen sulfide therapy suppresses cofilin-2 and attenuates ischemic heart failure in a mouse model of myocardial infarction. J Cardiovasc Pharmacol Ther. 2020;25(5):472–83. https://doi.org/10.1177/1074248420923542.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Wang L, Buckley AF, Spurney RF. Regulation of cofilin phosphorylation in glomerular podocytes by testis specific kinase 1 (TESK1). Sci Rep. 2018;8(1):12286. https://doi.org/10.1038/s41598-018-30115-3.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  19. Bamburg JR, Minamide LS, Wiggan O, Tahtamouni LH, Kuhn TB. Cofilin and actin dynamics: multiple modes of regulation and their impacts in neuronal development and degeneration. Cells. 2021;10(10):2726. https://doi.org/10.3390/cells10102726.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Sun Y, Liang L, Dong M, Li C, Liu Z, Gao H. Cofilin 2 in serum as a novel biomarker for Alzheimer’s Disease in Han Chinese. Front Aging Neurosci. 2019;11:214. https://doi.org/10.3389/fnagi.2019.00214.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Xu J, Huang Y, Zhao J, Wu L, Qi Q, Liu Y, et al. Cofilin: a promising protein implicated in cancer metastasis and apoptosis. Front Cell Dev Biol. 2021;9: 599065. https://doi.org/10.3389/fcell.2021.599065.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Backus BE, Six AJ, Kelder JH, Gibler WB, Moll FL, Doevendans PA. Risk scores for patients with chest pain: evaluation in the emergency department. Curr Cardiol Rev. 2011;7(1):2–8. https://doi.org/10.2174/157340311795677662.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Liu N, Ng JC, Ting CE, Sakamoto JT, Ho AF, Koh ZX, et al. Clinical scores for risk stratification of chest pain patients in the emergency department: an updated systemic review. J Emerg Crit Care Med. 2018;2:16. https://doi.org/10.21037/jeccm.2018.01.10.

    Article  Google Scholar 

  24. Hajian-Tilaki K. Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian J Intern Med. 2013;4(2):627–35.

    PubMed Central  PubMed  Google Scholar 

  25. Baumann AAW, Mishra A, Worthley MI, Nelson AJ, Psaltis PJ. Management of multivessel coronary artery disease in patients with non-ST-elevation myocardial infarction: a complex path to precision medicine. Ther Adv Chronic Dis. 2020;11:2040622320938527. https://doi.org/10.1177/2040622320938527.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Baumann AA, Tavella R, Air TM, Mishra A, Montarello NJ, Arstall M, et al. Prevalence and real-world management of NSTEMI with multivessel disease. Cardiovasc Diagn Ther. 2022;12(1):1–11. https://doi.org/10.21037/cdt-21-518.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Sharma YP, Santosh Vemuri K, Bootla D, Kanabar K, Pruthvi CR, Kaur N, et al. Epidemiological profile, management and outcomes of patients with acute coronary syndrome: single centre experience from a tertiary care hospital in North India. Indian Heart J. 2021;73(2):174–9. https://doi.org/10.1016/j.ihj.2020.11.149.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Wang D, Enck J, Howell BW, Olson EC. Ethanol exposure transiently elevates but persistently inhibits tyrosine kinase activity and impairs the growth of the nascent apical dendrite. Mol Neurobiol. 2019;56(8):5749–62. https://doi.org/10.1007/s12035-019-1473-x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Limatola N, Vasilev F, Santella L, Chun JT. Nicotine induces polyspermy in sea urchin eggs through a non-cholinergic pathway modulating actin dynamics. Cells. 2019;9(1):63. https://doi.org/10.3390/cells9010063.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Babes EE, Bustea C, Behl T, Abdel-Daim MM, Nechifor AC, Stoicescu M, et al. Acute coronary syndromes in diabetic patients, outcome, revascularization, and antithrombotic therapy. Biomed Pharmacother. 2022;148: 112772. https://doi.org/10.1016/j.biopha.2022.112772.

    Article  CAS  PubMed  Google Scholar 

  31. Dhungana SP, Mahato AK, Ghimire R, Shreewastav RK. Prevalence of dyslipidemia in patients with acute coronary syndrome admitted at tertiary care hospital in Nepal: A descriptive cross-sectional study. JNMA J Nepal Med Assoc. 2020;58(224):204–208. https://doi.org/10.31729/jnma.4765.

  32. Hien TT, Turczyńska KM, Dahan D, Ekman M, Grossi M, Sjögren J, et al. Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/Protein kinase C and actin polymerization. J Biol Chem. 2016;291(7):3552–68. https://doi.org/10.1074/jbc.M115.654384.

    Article  CAS  PubMed  Google Scholar 

  33. Hansson B, Morén B, Fryklund C, Vliex L, Wasserstrom S, Albinsson S, et al. Adipose cell size changes are associated with a drastic actin remodeling. Sci Rep. 2019;9:12941. https://doi.org/10.1038/s41598-019-49418-0.

    Article  ADS  CAS  PubMed Central  PubMed  Google Scholar 

  34. Sumi T, Matsumoto K, Takai Y, Nakamura T. Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2. J Cell Biol. 1999;147(7):1519–32. https://doi.org/10.1083/jcb.147.7.1519.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Gerbino A, Procino G, Svelto M, Carmosino M. Role of lamin A/C gene mutations in the signaling defects leading to cardiomyopathies. Front Physiol. 2018;9:1356. https://doi.org/10.3389/fphys.2018.01356.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Kueh HY, Charras GT, Mitchison TJ, Brieher WM. Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. J Cell Biol. 2008;182(2):341–53. https://doi.org/10.1083/jcb.200801027.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Yang FH, Pyle WG. Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning. J Mol Cell Cardiol. 2012;52(3):761–72.

    Article  CAS  PubMed  Google Scholar 

  38. Özdemİr A, Ark M. A novel ROCK inhibitor: off-target effects of metformin. Turk J Biol. 2021;45(1):35–45. https://doi.org/10.3906/biy-2004-12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Funding

This work was supported by an Intramural research grant from JIPMER, Puducherry, India (No: JIP/Res/Intramural/Phs 1/2021-22 dated May 20, 2021).

Author information

Authors and Affiliations

  1. Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India

    Ayush Kumar Ganguli & Prashant Shankarrao Adole

  2. Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India

    Kolar Vishwanath Vinod

Authors
  1. Ayush Kumar Ganguli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prashant Shankarrao Adole
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kolar Vishwanath Vinod
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.K.G. obtained patient data and blood samples, analyzed blood samples and data; P.S.A. designed the study, analyzed the data and contributed to the writing of the manuscript; K.V.V designed the study and contributed for the selection of study participants. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Prashant Shankarrao Adole.

Ethics declarations

Conflict of interest

None of the authors report any conflict of interest.

Ethics Approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Approval of the Institute Human Ethics Committee was taken (JIP/IEC/2021/014 Dated 03/03/2021). Written informed consent was taken from the study participants before recruitment and after informing them that the study was not part of their treatment.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ganguli, A.K., Adole, P.S. & Vinod, K.V. Exploring the Diagnostic Utility of Serum Cofilin-1 and 2 Levels in Patients with Acute Coronary Syndrome: A Case–Control Pilot Study. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01195-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12291-024-01195-y

Keywords

Search

Navigation