Skip to main content
Log in

Circulating miRNA as novel markers for diastolic dysfunction

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. Though their significance is unclear, pioneer profiling studies have attributed specific serum miRNA signatures to different disease conditions. The diagnostic potential of miRNA detection in human plasma for cardiovascular disorders is beginning to be recognized as important. In this study, we examined miRNA profiling in isolated diastolic dysfunction (DD) with preserved systolic function to identify promising candidate miRNAs. The presence of these miRNAs was tested in stable patients with isolated DD, patients with stable compensated dilated cardiomyopathy (DCM—systolic plus diastolic dysfunction) and those with decompensated congestive heart failure secondary to dilated cardiomyopathy (DCM–CHF—systolic plus diastolic dysfunction). We identified new circulating miRNAs (miR-454, miR-500, miR-1246, miR-142-3p) which showed distinct patterns of expression in patients with diastolic dysfunction. The presence or absence of systolic dysfunction does not seem to affect this trend. MiR-454 and miR-500 are downregulated in diastolic dysfunction. MiR-1246 is upregulated in diastolic dysfunction. MiR-142-3p is downregulated in DCM and DCM–CHF groups but not in the DD group. The expression of miR-124-5p is highly upregulated in DCM but not in DD and DCM–CHF groups. We therefore propose that these circulating miRNAs may serve as novel biomarkers for diastolic dysfunction because in all of these patients the only common factor was diastolic dysfunction.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  2. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP (2008) The impact of microRNAs on protein output. Nature 455:64–71

    Article  PubMed  CAS  Google Scholar 

  3. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63

    Article  PubMed  CAS  Google Scholar 

  4. Chien KR (2007) Molecular medicine: microRNAs and the tell-tale heart. Nature 447:389–390

    Article  PubMed  CAS  Google Scholar 

  5. Gupta R, Soni N, Patnaik P, Sood I, Singh R, Rawal K, Rani V (2010) High AU content: a signature of upregulated miRNA in cardiac diseases. Bioinformation 5:132–135

    Article  PubMed  Google Scholar 

  6. Zhao Y, Ransom JF, Li A, Vedantham V, von Drehle M, Muth AN, Tsuchihashi T, McManus MT, Schwartz RJ, Srivastava D (2007) Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1–2. Cell 129:303–317

    Article  PubMed  CAS  Google Scholar 

  7. Brattelid T, Aarnes EK, Helgeland E, Guvaag S, Eichele H, Jonassen AK (2011) Normalization strategy is critical for the outcome of miRNA expression analyses in the rat heart. Physiol Genomics 43:604–610

    Article  PubMed  CAS  Google Scholar 

  8. Wang J, Zheng Z, Lin FQ, Sun CC, Xu RX, Hu SS (2010) miRNA changes in the reverse remodeling heart of rats. Zhonghua xin xue guan bing za zhi [Chin J Cardiovasc Dis] 38:745–750

    CAS  Google Scholar 

  9. Lin RC, Weeks KL, Gao XM, Williams RB, Bernardo BC, Kiriazis H, Matthews VB, Woodcock EA, Bouwman RD, Mollica JP, Speirs HJ, Dawes IW, Daly RJ, Shioi T, Izumo S, Febbraio MA, Du XJ, McMullen JR (2010) PI3K(p110 alpha) protects against myocardial infarction-induced heart failure: identification of PI3K-regulated miRNA and mRNA. Arterioscler Thromb Vasc Biol 30:724–732

    Article  PubMed  CAS  Google Scholar 

  10. Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J, Li K, Yu B, Li Z, Wang R, Wang L, Li Q, Wang N, Shan H, Yang B (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 391:73–77

    Article  PubMed  CAS  Google Scholar 

  11. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506

    Article  PubMed  Google Scholar 

  12. Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T (2011) Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate the existence of myocardial damage. Circ Cardiovasc Genet 4(4):446–454

    Article  PubMed  CAS  Google Scholar 

  13. Cheng Y, Tan N, Yang J, Liu X, Cao X, He P, Dong X, Qin S, Zhang C (2010) A translational study of circulating cell-free microRNA-1 in acute myocardial infarction. Clin Sci 119:87–95

    Article  PubMed  CAS  Google Scholar 

  14. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q (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 

  15. Sucharov C, Bristow MR, Port JD (2008) miRNA expression in the failing human heart: functional correlates. J Mol Cell Cardiol 45:185–192

    Article  PubMed  CAS  Google Scholar 

  16. Miyachi M, Tsuchiya K, Yoshida H, Yagyu S, Kikuchi K, Misawa A, Iehara T, Hosoi H (2010) Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys Res Commun 400:89–93

    Article  PubMed  CAS  Google Scholar 

  17. Kosaka N, Iguchi H, Ochiya T (2010) Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci 101:2087–2092

    Article  PubMed  CAS  Google Scholar 

  18. Asaga S, Kuo C, Nguyen T, Terpenning M, Giuliano AE, Hoon DS (2011) Direct serum assay for microRNA-21 concentrations in early and advanced breast cancer. Clin Chem 57:84–91

    Article  PubMed  CAS  Google Scholar 

  19. Bianchi F, Nicassio F, Marzi M, Belloni E, Dall’olio V, Bernard L, Pelosi G, Maisonneuve P, Veronesi G, Di Fiore PP (2011) A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med 3(8):495–503

    Article  PubMed  CAS  Google Scholar 

  20. Liu R, Zhang C, Hu Z, Li G, Wang C, Yang C, Huang D, Chen X, Zhang H, Zhuang R, Deng T, Liu H, Yin J, Wang S, Zen K, Ba Y, Zhang CY (2011) A five-microRNA signature identified from genome-wide serum microRNA expression profiling serves as a fingerprint for gastric cancer diagnosis. Eur J Cancer 47:784–791

    Article  PubMed  CAS  Google Scholar 

  21. Cortez MA, Calin GA (2009) MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. Expert Opin Biol Ther 9:703–711

    Article  PubMed  CAS  Google Scholar 

  22. Tie Y, Liu B, Fu H, Zheng X (2009) Circulating miRNA and cancer diagnosis. Sci China Ser C 52:1117–1122

    Article  CAS  Google Scholar 

  23. Iborra M, Bernuzzi F, Invernizzi P, Danese S (2010) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11(5):305–314

    Article  PubMed  Google Scholar 

  24. Foss KM, Sima C, Ugolini D, Neri M, Allen KE, Weiss GJ (2011) miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer. J Thorac Oncol 6:482–488

    Article  PubMed  Google Scholar 

  25. Gui J, Tian Y, Wen X, Zhang W, Zhang P, Gao J, Run W, Tian L, Jia X, Gao Y (2011) Serum microRNA characterization identifies miR-885-5p as a potential marker for detecting liver pathologies. Clin Sci 120:183–193

    Article  PubMed  CAS  Google Scholar 

  26. Khan N, Cheng J, Pezacki JP, Berezovski MV (2011) Quantitative analysis of microRNA in blood serum with protein-facilitated affinity capillary electrophoresis. Anal Chem 83(16):6196–6201

    Article  PubMed  CAS  Google Scholar 

  27. Zahm AM, Thayu M, Hand NJ, Horner A, Leonard MB, Friedman JR (2011) Circulating microRNA is a biomarker of pediatric crohn disease. J Pediatr Gastroenterol Nutr 53:26–33

    Article  PubMed  CAS  Google Scholar 

  28. Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y, Nonogi H, Iwai N (2010) Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem 56:1183–1185

    Article  PubMed  CAS  Google Scholar 

  29. Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM (2010) MiR423-5p as a circulating biomarker for heart failure. Circ Res 106:1035–1039

    Article  PubMed  CAS  Google Scholar 

  30. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR, Rodeheffer RJ (2003) Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289:194–202

    Article  PubMed  Google Scholar 

  31. Cohen J, Cohen J (2003) Applied multiple regression/correlation analysis for the behavioral sciences. L. Erlbaum Associates, Mahwah

    Google Scholar 

  32. Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ (2009) Circulating microRNAs, potential biomarkers for drug-induced liver injury. Proc Natl Acad Sci USA 106:4402–4407

    Article  PubMed  CAS  Google Scholar 

  33. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433

    Article  PubMed  CAS  Google Scholar 

  34. Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L, Xiao T, Schafer J, Lee M-LT, Schmittgen TD, Nana-Sinkam SP, Jarjoura D, Marsh CB (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694

    Article  PubMed  Google Scholar 

  35. Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452

    Article  PubMed  CAS  Google Scholar 

  36. Laios A, O’Toole S, Flavin R, Martin C, Kelly L, Ring M, Finn SP, Barrett C, Loda M, Gleeson N, D’Arcy T, McGuinness E, Sheils O, Sheppard B, J OL (2008) Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer 7:35

    Article  PubMed  Google Scholar 

  37. Soper DS (2012) p value calculator for correlation coefficients (online software). http://www.danielsoper.com/statcalc3

Download references

Acknowledgments

This study was partly supported by start-up funds from the Texas A & M Health Science Center, College of Medicine, by an American Heart Association -National Scientist Development Grant (0835227 N) to S. Gupta (SG), and by a departmental grant from the Division of Cardiology, Scott & White Hospital (NN). We would like to thank Dr Gregory Dehmer for his time in reviewing this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Nandini Nair or Sudhiranjan Gupta.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 41 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nair, N., Kumar, S., Gongora, E. et al. Circulating miRNA as novel markers for diastolic dysfunction. Mol Cell Biochem 376, 33–40 (2013). https://doi.org/10.1007/s11010-012-1546-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-012-1546-x

Keywords

Navigation