Molecular and Cellular Biochemistry

, Volume 402, Issue 1–2, pp 171–180 | Cite as

Serum microRNA profiles in cats with hypertrophic cardiomyopathy

  • K. Weber
  • N. Rostert
  • S. Bauersachs
  • G. Wess


The role of microRNAs (miRNAs) in the pathogenesis of heart diseases of humans and rodents, as well as their diagnostic potential, has recently received much attention, but comparable studies for spontaneous disease models in the domestic cat are missing. Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. The pathology is largely unknown, but is suspected to be influenced by genetic background. In this study, we examined the miRNA profiles in the serum of cats with stable congestive heart failure caused by HCM (n = 11) and healthy control cats (n = 12) using miRNA arrays. 965 out of 2026 miRNAs could be detected in at least six samples of either of the groups. Eleven mammalian miRNAs were differentially expressed between the groups with a fold change ≥ 1.6. Hierarchical cluster analysis resulted in distinct separation of the two groups. After correction for multiple testing (adjusted p < 0.05), a higher expression of miR-381-3p, miR-486-3p, miR-4751, miR-476c-3p, miR-5700, miR-513a-3p, and miR-320e in the HCM group was confirmed. Additionally, miR-1246 was found to be upregulated 3-fold in the HCM group using quantitative RT-PCR. Software analysis of the significantly regulated miRNAs revealed 49 mRNA targets involved in cardiac hypertrophy. Cats with primary HCM show a distinct miRNA profile that includes miRNAs that have already been shown to be differentially regulated in human patients and rodent models for cardiac disease. Studying HCM as a spontaneous cardiac disease of the cat may help to reveal additional pathophysiologic pathways.


Biomarker Feline Heart disease Animal model Blood sample 



Nadine Rostert was granted a 2-year scholarship by the german ‘Akademie für Tiergesundheit’ for this project.

Conflict of interest


Supplementary material

11010_2014_2324_MOESM1_ESM.docx (42 kb)
Supplementary material 1 (DOCX 42 kb)
11010_2014_2324_MOESM2_ESM.docx (16 kb)
Supplementary material 2 (DOCX 16 kb)


  1. 1.
    Paige CF, Abbott JA, Elvinger F, Pyle RL (2009) Prevalence of cardiomyopathy in apparently healthy cats. J Am Vet Med Assoc 234:1398–1403CrossRefPubMedGoogle Scholar
  2. 2.
    Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D et al (2006) Contemporary definitions and classification of the cardiomyopathies: an American heart association scientific statement from the council on clinical cardiology, heart failure and transplantation committee; quality of care and outcomes research and functional genomics and translational biology interdisciplinary working groups; and council on epidemiology and prevention. Circulation 113:1807–1816CrossRefPubMedGoogle Scholar
  3. 3.
    Kittleson MD, Meurs KM, Munro MJ, Kittleson JA, Liu SK, Pion PD et al (1999) Familial hypertrophic cardiomyopathy in Maine Coon cats: an animal model of human disease. Circulation 99:3172–3180CrossRefPubMedGoogle Scholar
  4. 4.
    Fox PR, Liu SK, Maron BJ (1995) Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. An animal model of human disease. Circulation 92:2645–2651CrossRefPubMedGoogle Scholar
  5. 5.
    Braunwald E (2009) Hypertrophic cardiomyopathy: the early years. J Cardiovasc Transl Res 2:341–348CrossRefPubMedGoogle Scholar
  6. 6.
    Maron BJ, Spirito P, Wesley Y, Arce J (1986) Development and progression of left ventricular hypertrophy in children with hypertrophic cardiomyopathy. N Engl J Med 315:610–614CrossRefPubMedGoogle Scholar
  7. 7.
    Smith S, Dukes-McEwan J (2012) Clinical signs and left atrial size in cats with cardiovascular disease in general practice. J Small Anim Pract 53:27–33CrossRefPubMedGoogle Scholar
  8. 8.
    O’Mahony C, Elliott PM (2014) Prevention of sudden cardiac death in hypertrophic cardiomyopathy. Heart 100:254–260CrossRefPubMedGoogle Scholar
  9. 9.
    Liu SK, Roberts WC, Maron BJ (1993) Comparison of morphologic findings in spontaneously occurring hypertrophic cardiomyopathy in humans, cats and dogs. Am J Cardiol 72:944–951CrossRefPubMedGoogle Scholar
  10. 10.
    Trehiou-Sechi E, Tissier R, Gouni V, Misbach C, Petit AM, Balouka D et al (2012) Comparative echocardiographic and clinical features of hypertrophic cardiomyopathy in 5 breeds of cats: a retrospective analysis of 344 cases (2001–2011). J Vet Intern Med 26:532–541CrossRefPubMedGoogle Scholar
  11. 11.
    Rush JE, Freeman LM, Fenollosa NK, Brown DJ (2002) Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990–1999). J Am Vet Med Assoc 220:202–207CrossRefPubMedGoogle Scholar
  12. 12.
    Meurs KM, Sanchez X, David RM, Bowles NE, Towbin JA, Reiser PJ et al (2005) A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet 14:3587–3593CrossRefPubMedGoogle Scholar
  13. 13.
    Meurs KM, Norgard MM, Ederer MM, Hendrix KP, Kittleson MD (2007) A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics 90:261–264CrossRefPubMedGoogle Scholar
  14. 14.
    Wess G, Schinner C, Weber K, Kuchenhoff H, Hartmann K (2010) Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine Coon and other breed cats. J Vet Intern Med 24:527–532CrossRefPubMedGoogle Scholar
  15. 15.
    Longeri M, Ferrari P, Knafelz P, Mezzelani A, Marabotti A, Milanesi L et al (2013) Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with hypertrophic cardiomyopathy. J Vet Intern Med 27:275–285CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Liu N, Olson EN (2010) MicroRNA regulatory networks in cardiovascular development. Dev Cell 18:510–525CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Ikeda S, Kong SW, Lu J, Bisping E, Zhang H, Allen PD et al (2007) Altered microRNA expression in human heart disease. Physiol Genomics 31:367–373CrossRefPubMedGoogle Scholar
  18. 18.
    Latronico MV, Catalucci D, Condorelli G (2008) MicroRNA and cardiac pathologies. Physiol Genomics 34:239–242CrossRefPubMedGoogle Scholar
  19. 19.
    Kuster DW, Mulders J, Ten Cate FJ, Michels M, Dos Remedios CG, da Costa Martins PA et al (2013) MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy patients with MYBPC3 mutations. J Mol Cell Cardiol 65:59–66CrossRefPubMedGoogle Scholar
  20. 20.
    Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L et al (2010) Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506CrossRefPubMedGoogle Scholar
  21. 21.
    Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N (2011) Assessment of plasma miRNAs in congestive heart failure. Circ J 75:336–340CrossRefPubMedGoogle Scholar
  22. 22.
    Vignier N, Amor F, Fogel P, Duvallet A, Poupiot J, Charrier S et al (2013) Distinctive serum miRNA profile in mouse models of striated muscular pathologies. PLoS One 8:e55281CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Nair N, Kumar S, Gongora E, Gupta S (2013) Circulating miRNA as novel markers for diastolic dysfunction. Mol Cell Biochem 376:33–40CrossRefPubMedGoogle Scholar
  24. 24.
    Huber W, von Heydebreck A, Sultmann H, Poustka A, Vingron M (2002) Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18(Suppl 1):S96–S104CrossRefPubMedGoogle Scholar
  25. 25.
    Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: Article 3Google Scholar
  26. 26.
    Saeed AI, Sharov V, White J, Li J, Liang W, Bhagabati N et al (2003) TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34:374–378PubMedGoogle Scholar
  27. 27.
    Satoh M, Minami Y, Takahashi Y, Tabuchi T, Nakamura M (2010) Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy. J Card Fail 16:404–410CrossRefPubMedGoogle Scholar
  28. 28.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006CrossRefPubMedGoogle Scholar
  30. 30.
    Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21CrossRefPubMedGoogle Scholar
  31. 31.
    Ai J, Zhang R, Li Y, Pu J, Lu Y, Jiao J et al (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochem Biophys Res Commun 391:73–77CrossRefPubMedGoogle Scholar
  32. 32.
    Ji X, Takahashi R, Hiura Y, Hirokawa G, Fukushima Y, Iwai N (2009) Plasma miR-208 as a biomarker of myocardial injury. Clin Chem 55:1944–1949CrossRefPubMedGoogle Scholar
  33. 33.
    Adachi T, Nakanishi M, Otsuka Y, Nishimura K, Hirokawa G, Goto Y et al (2010) Plasma microRNA 499 as a biomarker of acute myocardial infarction. Clin Chem 56:1183–1185CrossRefPubMedGoogle Scholar
  34. 34.
    Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J et al (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31:659–666CrossRefPubMedGoogle Scholar
  35. 35.
    Feng HJ, Ouyang W, Liu JH, Sun YG, Hu R, Huang LH et al (2014) Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy. Braz J Med Biol Res 47:361–368CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE et al (2010) MiR423-5p as a circulating biomarker for heart failure. Circ Res 106:1035–1039CrossRefPubMedGoogle Scholar
  37. 37.
    Sathyamurthy G, Swamy NR (2010) Computational identification of putative miRNAs from Felis Catus. Biomed Eng Comput Biol 2:37–46Google Scholar
  38. 38.
    Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW et al (2007) MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 116:258–267CrossRefPubMedGoogle Scholar
  39. 39.
    Leptidis S, El Azzouzi H, Lok SI, de Weger R, Olieslagers S, Kisters N et al (2013) A deep sequencing approach to uncover the miRNOME in the human heart. PLoS ONE 8:e57800CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Xiao J, Liang D, Zhang Y, Liu Y, Zhang H, Liu Y et al (2011) MicroRNA expression signature in atrial fibrillation with mitral stenosis. Physiol Genomics 43:655–664CrossRefPubMedGoogle Scholar
  41. 41.
    Hasdemir C, Aydin HH, Celik HA, Simsek E, Payzin S, Kayikcioglu M et al (2010) Transcriptional profiling of septal wall of the right ventricular outflow tract in patients with idiopathic ventricular arrhythmias. Pacing Clin Electrophysiol 33:159–167CrossRefPubMedGoogle Scholar
  42. 42.
    Cooley N, Cowley MJ, Lin RC, Marasco S, Wong C, Kaye DM et al (2012) Influence of atrial fibrillation on microRNA expression profiles in left and right atria from patients with valvular heart disease. Physiol Genomics 44:211–219CrossRefPubMedGoogle Scholar
  43. 43.
    Schulte JS, Seidl MD, Nunes F, Freese C, Schneider M, Schmitz W et al (2012) CREB critically regulates action potential shape and duration in the adult mouse ventricle. Am J Physiol Heart Circ Physiol 302:H1998–H2007CrossRefPubMedGoogle Scholar
  44. 44.
    Tritsch E, Mallat Y, Lefebvre F, Diguet N, Escoubet B, Blanc J et al (2013) An SRF/miR-1 axis regulates NCX1 and annexin A5 protein levels in the normal and failing heart. Cardiovasc Res 98:372–380CrossRefPubMedGoogle Scholar
  45. 45.
    Laustsen PG, Russell SJ, Cui L, Entingh-Pearsall A, Holzenberger M, Liao R et al (2007) Essential role of insulin and insulin-like growth factor 1 receptor signaling in cardiac development and function. Mol Cell Biol 27:1649–1664CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Gupta MK, Halley C, Duan ZH, Lappe J, Viterna J, Jana S et al (2013) miRNA-548c: a specific signature in circulating PBMCs from dilated cardiomyopathy patients. J Mol Cell Cardiol 62:131–141CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Hunter MP, Ismail N, Zhang X, Aguda BD, Lee EJ, Yu L et al (2008) Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3:e3694CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Chim SS, Shing TK, Hung EC, Leung TY, Lau TK, Chiu RW et al (2008) Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 54:482–490CrossRefPubMedGoogle Scholar
  49. 49.
    Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N et al (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3:e3148CrossRefPubMedCentralPubMedGoogle Scholar
  50. 50.
    Noren Hooten N, Fitzpatrick M, Wood WH 3rd, De S, Ejiogu N, Zhang Y et al (2013) Age-related changes in microRNA levels in serum. Aging (Albany NY) 5:725–740Google Scholar
  51. 51.
    Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O (2012) Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 14:147–154CrossRefPubMedGoogle Scholar
  52. 52.
    Dickinson BA, Semus HM, Montgomery RL, Stack C, Latimer PA, Lewton SM et al (2013) Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure. Eur J Heart Fail 15:650–659CrossRefPubMedGoogle Scholar
  53. 53.
    Reid G, Kirschner MB, van Zandwijk N (2011) Circulating microRNAs: association with disease and potential use as biomarkers. Crit Rev Oncol Hematol 80:193–208CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • K. Weber
    • 1
  • N. Rostert
    • 1
    • 2
    • 3
  • S. Bauersachs
    • 2
    • 3
  • G. Wess
    • 1
  1. 1.Faculty of Veterinary Medicine, Clinic of Small Animal Medicine, Centre for Clinical Veterinary MedicineLMU MunichMunichGermany
  2. 2.Laboratory for Functional Genome Analysis (LAFUGA), Gene CenterLMU MunichMunichGermany
  3. 3.Institute of Agricultural Sciences, Animal PhysiologyETH ZurichZurichSwitzerland

Personalised recommendations