Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: LCK: a new biomarker candidate for the early diagnosis of acute myocardial infarction

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

This article was retracted on 18 August 2015

Abstract

Acute myocardial infarction (AMI) is one of the most common cardiovascular emergencies, of which the molecular pathogenesis is still not fully understood. This study aimed to explore the differentially expressed genes (DEGs) and then identify the critical genes in AMI thus screening out potential biomarkers for the early diagnosis of this serious heart disease. The gene expression data of AMI patients (GSE19339) were downloaded from gene expression omnibus database. After preprocessing with affy package, the DEGs were screened out by significance analysis of microarray (SAM) algorithm within samr package. Then function and pathway enrichment analyses of the DEGs were carried out using DAVID (database for annotation visualization and integrated discovery software) online tools. Further, the relevant genes of AMI were screened out with GENETIC_ASSOCIATION_DB_DISEASE analysis and blastp alignment. Finally, the novel genes were subjected to transcription factor and protein–protein interaction network analyses. A total of 633 DEGs, including 378 up-regulated and 255 down-regulated, were screened out between AMI patients and normal control samples. Among those genes, several important ones such as PPAR, CCL2, HMOX1 and NPR1 were demonstrated to be related to AMI. Most importantly, a novel gene LCK (lymphocyte-specific protein tyrosine kinase) was significantly differentially expressed in AMI. Further analyses showed that LCK was involved in the expression regulation of CXCL12 (chemokine (C-X-C motif) ligand 12) and the expression of LCK can be regulated by different transcription factors. In this study, we provided a new insight into the mechanism of AMI and raised LCK as an attractive marker candidate in the diagnosis of this serious heart disease.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Daubert MA, Jeremias A (2010) The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manag 6:691

    PubMed Central  CAS  PubMed  Google Scholar 

  2. Boersma E, Mercado N, Poldermans D, Gardien M, Vos J, Simoons ML (2003) Acute myocardial infarction. Lancet 361:847–858

    Article  PubMed  Google Scholar 

  3. He J, Gu D, Wu X et al (2005) Major causes of death among men and women in China. N Engl J Med 353:1124–1134

    Article  CAS  PubMed  Google Scholar 

  4. Sanderson JE, Mayosi B, Yusuf S, Reddy S, Hu S, Chen Z, Timmis A (2007) Global burden of cardiovascular disease. Heart 93:1175

    Article  PubMed Central  PubMed  Google Scholar 

  5. Lloyd-Jones D, Adams R, Carnethon M et al (2009) Heart disease and stroke statistics—2009 update a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119:e21–e181

    Article  PubMed  Google Scholar 

  6. Caligiuri G, Nicoletti A (2006) Lymphocyte responses in acute coronary syndromes: lack of regulation spawns deviant behaviour. Eur Heart J 27:2485–2486

    Article  PubMed  Google Scholar 

  7. Recchioni R, Marcheselli F, Olivieri F, Ricci S, Procopio AD, Antonicelli R (2013) Conventional and novel diagnostic biomarkers of acute myocardial infarction: a promising role for circulating microRNAs. Biomarkers 18:547–558

    Article  CAS  PubMed  Google Scholar 

  8. Jaffe AS, Babuin L, Apple FS (2006) Biomarkers in acute cardiac diseasethe present and the future. J Am Coll Cardiol 48:1–11

    Article  CAS  PubMed  Google Scholar 

  9. Gerhardt W, Nordin G, Ljungdahl L (1999) Can Troponin T replace CK MBmass as “gold standard” for Acute Myocardial Infarction (“AMI”)? Scand J Clin Lab Inv 59:83–89

    Article  CAS  Google Scholar 

  10. Morrow DA, Cannon CP, Jesse RL et al (2007) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem 53:552–574

    Article  CAS  PubMed  Google Scholar 

  11. Wang G-K, Zhu J-Q, Zhang J-T et al (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31:659–666

    Article  PubMed  Google Scholar 

  12. Barrett T, Wilhite SE, Ledoux P et al (2013) NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res 41:D991–D995

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Gentleman RC, Carey VJ, Bates DM et al (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5:R80

    Article  PubMed Central  PubMed  Google Scholar 

  14. Schwender H, Krause A, Ickstadt K (2006) Identifying interesting genes with siggenes. The Newsletter of the R Project Vol 6/5, December 2006 34:45

  15. Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3

    Article  PubMed  Google Scholar 

  16. Punta M, Coggill PC, Eberhardt RY et al (2012) The Pfam protein families database. Nucleic Acids Res 40:D290–D301

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Frazer KA, Pachter L, Poliakov A, Rubin EM, Dubchak I (2004) VISTA: computational tools for comparative genomics. Nucleic Acids Res 32:W273–W279

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Szklarczyk D, Franceschini A, Kuhn M et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39:D561–D568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T (2011) Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics 27:431–432

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Bernardes A, Souza PC, Muniz JR et al (2013) Molecular mechanism of peroxisome proliferator-activated receptor α activation by WY14643: a new mode of ligand recognition and receptor stabilization. J Mol Biol 425:2878–2893

    Article  CAS  PubMed  Google Scholar 

  21. Braissant O, Foufelle F, Scotto C, Dauça M, Wahli W (1996) Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha,-beta, and-gamma in the adult rat. Endocrinology 137:354–366

    CAS  PubMed  Google Scholar 

  22. Doney A, Fischer B, Lee SP, Morris AD, Leese G, Palmer C (2005) Association of common variation in the PPARA gene with incident myocardial infarction in individuals with type 2 diabetes: a Go-DARTS study. Nucl Recept 3:4

    Article  PubMed Central  PubMed  Google Scholar 

  23. Nikitin AG, Chistiakov DA, Minushkina LO, Zateyshchikov DA, Nosikov VV (2010) Association of the CYBA, PPARGC1A, PPARG3, and PPARD gene variants with coronary artery disease and metabolic risk factors of coronary atherosclerosis in a Russian population. Heart Vessels 25:229–236

    Article  PubMed  Google Scholar 

  24. Hamilton ST, Scott GM, Naing Z, Rawlinson WD (2013) Human cytomegalovirus directly modulates expression of chemokine CCL2 (MCP-1) during viral replication. J Gen Virol 94:2495–2503

    Article  CAS  PubMed  Google Scholar 

  25. Ikeda U, Matsui K, Murakami Y, Shimada K (2002) Monocyte chemoattractant protein-1 and coronary artery disease. Clin Cardiol 25:143–147

    Article  PubMed  Google Scholar 

  26. Boring L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in CCR2 −/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897

    Article  CAS  PubMed  Google Scholar 

  27. Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor–deficient mice. Mol Cell 2:275–281

    Article  CAS  PubMed  Google Scholar 

  28. Aiello RJ, PAK Bourassa, Lindsey S, Weng W, Natoli E, Rollins BJ, Milos PM (1999) Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 19:1518–1525

    Article  CAS  PubMed  Google Scholar 

  29. Devaux Y, Azuaje F, Vausort M, Yvorra C, Wagner DR (2010) Integrated protein network and microarray analysis to identify potential biomarkers after myocardial infarction. Funct Integr Genomics 10:329–337

    Article  CAS  PubMed  Google Scholar 

  30. Ishikawa K, Maruyama Y (2000) Heme oxygenase as an intrinsic defense system in vascular wall: implication against atherogenesis. J Atheroscler Thromb 8:63–70

    Article  Google Scholar 

  31. Ono K, Goto Y, Takagi S, Baba S, Tago N, Nonogi H, Iwai N (2004) A promoter variant of the heme oxygenase-1 gene may reduce the incidence of ischemic heart disease in Japanese. Atherosclerosis 173:313–317

    Article  Google Scholar 

  32. Richards AM, Nicholls MG, Espiner EA et al (2003) B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation 107:2786–2792

    Article  CAS  PubMed  Google Scholar 

  33. Marth JD, Disteche C, Pravtcheva D, Ruddle F, Krebs EG, Perlmutter RM (1986) Localization of a lymphocyte-specific protein tyrosine kinase gene (lck) at a site of frequent chromosomal abnormalities in human lymphomas. Proc Natl Acad Sci USA 83:7400–7404

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Ping P, Zhang J, Zheng Y-T et al (1999) Demonstration of selective protein kinase C–dependent activation of Src and Lck tyrosine kinases during ischemic preconditioning in conscious rabbits. Circ Res 85:542–550

    Article  CAS  PubMed  Google Scholar 

  35. Baines CP, Wang L, Cohen MV, Downey JM (1998) Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning’s anti-infarct effect in the rabbit heart. J Mol Cell Cardiol 30:383–392

    Article  CAS  PubMed  Google Scholar 

  36. Ping P, Song C, Zhang J et al (2002) Formation of protein kinase Cε-Lck signaling modules confers cardioprotection. J Clin Invest 109:499–507

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Wright DD, Sefton BM, Kamps MP (1994) Oncogenic activation of the Lck protein accompanies translocation of the LCK gene in the human HSB2 T-cell leukemia. Mol Cell Biol 14:2429–2437

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Talab F, Allen JC, Thompson V, Lin K, Slupsky JR (2013) LCK is an important mediator of B-cell receptor signaling in chronic lymphocytic leukemia cells. Mol Cancer Res 11:541–554

    Article  CAS  PubMed  Google Scholar 

  39. Paterson JC, Tedoldi S, Craxton A et al (2006) The differential expression of LCK and BAFF-receptor and their role in apoptosis in human lymphomas. Haematologica 91:772–780

    CAS  PubMed  Google Scholar 

  40. Rhee I, Veillette A (2012) Protein tyrosine phosphatases in lymphocyte activation and autoimmunity. Nat Immunol 13:439–447

    Article  CAS  PubMed  Google Scholar 

  41. Blum A, Yeganeh S (2003) The role of T-lymphocyte subpopulations in acute myocardial infarction. Eur J Intern Med 14:407–410

    Article  CAS  PubMed  Google Scholar 

  42. Bodi V, Sanchis J, Nunez J et al (2008) Uncontrolled immune response in acute myocardial infarction: unraveling the thread. Am Heart J 156:1065–1073

    Article  CAS  PubMed  Google Scholar 

  43. Inngjerdingen M, Torgersen KM, Maghazachi AA (2002) Lck is required for stromal cell–derived factor 1α (CXCL12)–induced lymphoid cell chemotaxis. Blood 99:4318–4325

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by National Natural Science Foundation of China (81270302), PUMC Youth Fund (2012-XHQN08), and Fuwai science &technology star project (2012-FWXX05).

Author information

Authors and Affiliations

  1. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing, 100037, China

    Fei Xu, Xiao Teng, Xin Yuan, Jiakang Sun, Hengchao Wu, Zhe Zheng, Yue Tang & Shengshou Hu

  2. Department of Surgery, Center for Regenerative Medicine, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 167A Beilishi Road, Xicheng District, 100037, Beijing, China

    Fei Xu, Xin Yuan, Jiakang Sun, Hengchao Wu, Zhe Zheng, Yue Tang & Shengshou Hu

  3. Zoopery Center, Fuwai Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100037, China

    Yue Tang

Authors
  1. Fei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xin Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiakang Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hengchao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhe Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yue Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shengshou Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xin Yuan.

Additional information

Co-first authors: Fei Xu and Xiao Teng.

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, F., Teng, X., Yuan, X. et al. RETRACTED ARTICLE: LCK: a new biomarker candidate for the early diagnosis of acute myocardial infarction. Mol Biol Rep 41, 8047–8053 (2014). https://doi.org/10.1007/s11033-014-3702-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3702-8

Keywords

Search

Navigation