Skip to main content
SpringerLink
Log in

Unraveling the exercise-related proteome signature in heart

  • Review
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Exercise training is a well-known non-pharmacological strategy for the prevention and treatment of cardiovascular diseases. Despite the established phenotypic knowledge, the molecular signature of exercise-induced cardiac remodeling remains poorly characterized. The great majority of studies dedicated to this topic use conventional reductionist methods, which only allow analyzing individual protein candidates. Nowadays, several methodologies based on mass spectrometry are available and have been successfully applied for the characterization of heart proteome, representing an attractive approach for the wide characterization of the complex molecular networks that underlie exercise-induced cardiac remodeling. Still, few studies have used these methodologies to understand the impact of exercise training on the remodeling of cardiac proteome. The present study analyzes the few available data obtained from mass spectrometry (MS)-based proteomic studies assessing the impact of distinct types of exercise training on the protein profile of heart (left ventricle and isolated mitochondria) and the potential cross-tolerance between exercise training and diseases as myocardial infarction and obesity. Network analysis was performed with bioinformatics to integrate data from distinct research papers, based on distinct exercise training protocols, animal models and methodological approaches applied in the characterization of heart proteome. The analysis revealed that exercise training confers a unique proteome signature characterized by the up-regulation of lipid and organic metabolic processes, vasculogenesis and tissue regeneration. Data retrieved from this analysis also suggested that cardiac mitochondrial proteome is highly dynamic in response to exercise training due, in part, to the action of specific kinases as PKA and PKG. Regarding to the type of exercise, treadmill training seems to have a greater effect on the modulation of cardiac proteome than swimming. Data from the present review will certainly open new perspectives on cardiac proteomics and will help to envisage future studies targeting the identification of the regulatory mechanisms underlying cardiac adaptive and maladaptive remodeling.

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. Abdallah C, Dumas-Gaudot E, Renaut J, Sergeant K (2012) Gel-based and gel-free quantitative proteomics approaches at a glance. Int J Plant Genomics 2012:494572. doi:10.1155/2012/494572

    PubMed Central  PubMed  Google Scholar 

  2. Anversa P, Beghi C, Levicky V, McDonald SL, Kikkawa Y, Olivetti G (1985) Effects of strenuous exercise on the quantitative morphology of left ventricular myocardium in the rat. J Mol Cell Cardiol 17:587–595. doi:10.1016/s0022-2828(85)80027-4

    CAS  PubMed  Google Scholar 

  3. Ascensão A, Magalhães J, Soares J, Ferreira R, Neuparth M, Marques F, Oliveira P, Duarte J (2005) Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis. Am J Physiol Heart Circ Physiol. doi:10.1152/ajpheart.01249.2004

    PubMed  Google Scholar 

  4. Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (2003) Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880. doi:10.1161/01.RES.0000069215.36389.8D

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Bansal A, Dai Q, Chiao YA, Hakala KW, Zhang JQ, Weintraub ST, Lindsey ML (2010) Proteomic analysis reveals late exercise effects on cardiac remodeling following myocardial infarction. J Proteomics 73:2041–2049. doi:10.1016/j.jprot.2010.06.009

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Beadle RM, Frenneaux M (2010) Modification of myocardial substrate utilisation: a new therapeutic paradigm in cardiovascular disease. Heart 96:824–830. doi:10.1136/hrt.2009.190256

    CAS  PubMed  Google Scholar 

  7. Bellafiore M, Sivverini G, Palumbo D, Macaluso F, Bianco A, Palma A, Farina F (2007) Increased cx43 and angiogenesis in exercised mouse hearts. Int J Sports Med 28:749–755. doi:10.1055/s-2007-964899

    CAS  PubMed  Google Scholar 

  8. Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabe-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisen J (2009) Evidence for cardiomyocyte renewal in humans. Science 324:98–102. doi:10.1126/science.1164680

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pages F, Trajanoski Z, Galon J (2009) ClueGO: a Cytoscape plug-into decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093. doi:10.1093/bioinformatics/btp101

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Boluyt MO, Brevick JL, Rogers DS, Randall MJ, Scalia AF, Li ZB (2006) Changes in the rat heart proteome induced by exercise training: increased abundance of heat shock protein hsp20. Proteomics 6:3154–3169. doi:10.1002/pmic.200401356

    CAS  PubMed  Google Scholar 

  11. Boudina S, Sena S, O’Neill BT, Tathireddy P, Young ME, Abel ED (2005) Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circ 112:2686–2695. doi:10.1161/CIRCULATIONAHA.105.554360

    Google Scholar 

  12. Brewis IA, Brennan P (2010) Proteomics technologies for the global identification and quantification of proteins. Adv Protein Chem Struct Biol 80:1–44. doi:10.1016/B978-0-12-381264-3.00001-1

    CAS  PubMed  Google Scholar 

  13. Brinkmann C, Brixius K (2013) Peroxiredoxins and sports: new insights on the antioxidative defense. J Physiol Sci JPS 63:1–5. doi:10.1007/s12576-012-0237-4

    CAS  Google Scholar 

  14. Broderick TL, Wang D, Jankowski M, Gutkowska J (2014) Unexpected effects of voluntary exercise training on natriuretic peptide and receptor mRNA expression in the ob/ob mouse heart. Regul Pept 188:52–59. doi:10.1016/j.regpep.2013.12.005

    CAS  PubMed  Google Scholar 

  15. Brown DA, Chicco AJ, Jew KN, Johnson MS, Lynch JM, Watson PA, Moore RL (2005) Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat. J Physiol 569:913–924. doi:10.1113/jphysiol.2005.095729

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Brown DA, Jew KN, Sparagna GC, Musch TI, Moore RL (2003) Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart. J Appl Physiol 95:2510–2518. doi:10.1152/japplphysiol.00487.2003

    PubMed  Google Scholar 

  17. Brown RD, Ambler SK, Mitchell MD, Long CS (2005) The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol 45:657–687. doi:10.1146/annurev.pharmtox.45.120403.095802

    CAS  PubMed  Google Scholar 

  18. Buermans HPJ, Redout EM, Schiel AE, Musters RJP, Zuidwijk M, Eijk PP, van Hardeveld C, Kasanmoentalib S, Visser FC, Ylstra B, Simonides WS (2005) Microarray analysis reveals pivotal divergent mRNA expression profiles early in the development of either compensated ventricular hypertrophy or heart failure. Physiol Genomics 21:314–323. doi:10.1152/physiolgenomics.00185.2004

    CAS  PubMed  Google Scholar 

  19. Burgess MW, Keshishian H, Mani DR, Gillette MA, Carr SA (2014) Simplified and efficient quantification of low-abundance proteins at very high multiplex via targeted mass spectrometry. Mol Cell Proteomics 13:1137–1149. doi:10.1074/mcp.M113.034660

    CAS  PubMed  Google Scholar 

  20. Burniston JG (2009) Adaptation of the rat cardiac proteome in response to intensity-controlled endurance exercise. Proteomics 9:106–115. doi:10.1002/pmic.200800268

    CAS  PubMed  Google Scholar 

  21. Chen Y, Cao X (2009) NFAT directly regulates Nk2–5 transcription during cardiac cell differentiation. Biol Cell 101:335–349. doi:10.1042/BC20080108

    CAS  PubMed  Google Scholar 

  22. Chevalier F (2010) Highlights on the capacities of “Gel-based” proteomics. Proteome Sci 8:23. doi:10.1186/1477-5956-8-23

    PubMed Central  PubMed  Google Scholar 

  23. Chugh S, Suen C, Gramolini A (2010) Proteomics and mass spectrometry: what have we learned about the heart? Curr Cardiol Rev 6:124–133. doi:10.2174/157340310791162631

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Cohen-Solal A, Leclercq C, Deray G, Lasocki S, Zambrowski JJ, Mebazaa A, de Groote P, Damy T, Galinier M (2014) Iron deficiency: an emerging therapeutic target in heart failure. Heart. doi:10.1136/heartjnl-2014-305669

    PubMed  Google Scholar 

  25. Cohn JN, Ferrari R, Sharpe N (2000) Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol 35:569–582

    CAS  PubMed  Google Scholar 

  26. Das H, George JC, Joseph M, Das M, Abdulhameed N, Blitz A, Khan M, Sakthivel R, Mao HQ, Hoit BD, Kuppusamy P, Pompili VJ (2009) Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model. PLoS ONE 4:e7325. doi:10.1371/journal.pone.0007325

    PubMed Central  PubMed  Google Scholar 

  27. de Boer RA, Pinto YM, van Veldhuisen DJ (2003) The Imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities. Microcirculation 10:113–126. doi:10.1038/sj.mn.7800188

    PubMed  Google Scholar 

  28. Di Silvestre D, Brambilla F, Mauri PL (2013) Multidimensional protein identification technology for direct-tissue proteomics of heart. Methods Mol Biol 1005:25–38. doi:10.1007/978-1-62703-386-2_3

    PubMed  Google Scholar 

  29. Didangelos A, Yin X, Mayr M (2012) Method for protein subfractionation of cardiovascular tissues before DIGE analysis. Methods Mol Biol 854:287–297. doi:10.1007/978-1-61779-573-2_20

    CAS  PubMed  Google Scholar 

  30. Diez J, Gonzalez A, Lopez B, Querejeta R (2005) Mechanisms of disease: pathologic structural remodeling is more than adaptive hypertrophy in hypertensive heart disease. Nature clinical practice. Cardiovasc Med 2:209–216. doi:10.1038/ncpcardio0158

    CAS  Google Scholar 

  31. Ellison GM, Waring CD, Vicinanza C, Torella D (2012) Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms. Heart 98:5–10. doi:10.1136/heartjnl-2011-300639

    CAS  PubMed  Google Scholar 

  32. Fan GC, Chu G, Kranias EG (2005) Hsp20 and its cardioprotection. Trends Cardiovasc Med 15:138–141. doi:10.1016/j.tcm.2005.05.004

    CAS  PubMed  Google Scholar 

  33. Fan GC, Kranias EG (2011) Small heat shock protein 20 (HspB6) in cardiac hypertrophy and failure. J Mol Cell Cardiol 51:574–577. doi:10.1016/j.yjmcc.2010.09.013

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Ferreira R, Vitorino R, Alves RM, Appell HJ, Powers SK, Duarte JA, Amado F (2010) Subsarcolemmal and intermyofibrillar mitochondria proteome differences disclose functional specializations in skeletal muscle. Proteomics 10:3142–3154. doi:10.1002/pmic.201000173

    CAS  PubMed  Google Scholar 

  35. Ferreira R, Vitorino R, Padrao AI, Espadas G, Mancuso FM, Moreira-Goncalves D, Castro-Sousa G, Henriques-Coelho T, Oliveira PA, Barros AS, Duarte JA, Sabido E, Amado F (2014) Lifelong exercise training modulates cardiac mitochondrial phosphoproteome in rats. J Proteome Res 13:2045–2055. doi:10.1021/pr4011926

    CAS  PubMed  Google Scholar 

  36. Frey N, Katus HA, Olson EN, Hill JA (2004) Hypertrophy of the heart: a new therapeutic target? Circulation 109:1580–1589. doi:10.1161/01.CIR.0000120390.68287.BB109/13/1580

    PubMed  Google Scholar 

  37. Gillet LC, Navarro P, Tate S, Rost H, Selevsek N, Reiter L, Bonner R, Aebersold R (2012) Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics 11(O111):016717. doi:10.1074/mcp.O111.016717

    PubMed  Google Scholar 

  38. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB (2014) Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129:399–410. doi:10.1161/01.cir.0000442015.53336.12

    PubMed  Google Scholar 

  39. Gonzalez-Loyola A, Barba I (2010) Mitochondrial metabolism revisited: a route to cardioprotection. Cardiovasc Res 88:209–210. doi:10.1093/cvr/cvq258

    CAS  PubMed  Google Scholar 

  40. Gorg A, Weiss W, Dunn MJ (2004) Current two-dimensional electrophoresis technology for proteomics. Proteomics 4:3665–3685. doi:10.1002/pmic.200401031

    PubMed  Google Scholar 

  41. Gregorich ZR, Chang YH, Ge Y (2014) Proteomics in heart failure: top-down or bottom-up? Pflug Arch. doi:10.1007/s00424-014-1471-9

    Google Scholar 

  42. Gu HJ, Gao CB, Gong JL, Li XJ, Sun B, Li XN (2012) Comparative proteomic analysis in left ventricular remodeling following myocardial infarction in rats. Biomed Environ Sci 25:117–123. doi:10.3967/0895-3988.2012.01.017

    CAS  PubMed  Google Scholar 

  43. Heusch G, Libby P, Gersh B, Yellon D, Bohm M, Lopaschuk G, Opie L (2014) Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383:1933–1943. doi:10.1016/S0140-6736(14)60107-0

    PubMed  Google Scholar 

  44. Iemitsu M, Maeda S, Jesmin S, Otsuki T, Kasuya Y, Miyauchi T (2006) Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise. J Appl Physiol 101:151–163. doi:10.1152/japplphysiol.00392.2005

    CAS  PubMed  Google Scholar 

  45. Javadov S, Jang S, Agostini B (2014) Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: therapeutic perspectives. Pharmacol Ther. doi:10.1016/j.pharmthera.2014.05.013

    PubMed  Google Scholar 

  46. Jin YF, Han HC, Berger J, Dai Q, Lindsey ML (2011) Combining experimental and mathematical modeling to reveal mechanisms of macrophage-dependent left ventricular remodeling. BMC Syst Biol 5:60. doi:10.1186/1752-0509-5-60

    PubMed Central  PubMed  Google Scholar 

  47. Kavazis AN, Alvarez S, Talbert E, Lee Y, Powers SK (2009) Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins. Am J Physiol Heart Circ Physiol 297:H144–H152. doi:10.1152/ajpheart.01278.2008

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Kavazis AN, McClung JM, Hood DA, Powers SK (2008) Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli. Am J Physiol Heart Circ Physiol 294:H928–H935. doi:10.1152/ajpheart.01231.2007

    CAS  PubMed  Google Scholar 

  49. Keshishian H, Addona T, Burgess M, Mani DR, Shi X, Kuhn E, Sabatine MS, Gerszten RE, Carr SA (2009) Quantification of cardiovascular biomarkers in patient plasma by targeted mass spectrometry and stable isotope dilution. Mol Cell Proteomics 8:2339–2349. doi:10.1074/mcp.M900140-MCP200

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Kline KG, Wu CC (2009) MudPIT analysis: application to human heart tissue. Methods Mol Biol 528:281–293. doi:10.1007/978-1-60327-310-7_20

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Konstam MA, Udelson JE, Anand IS, Cohn JN (2003) Ventricular remodeling in heart failure: a credible surrogate endpoint. J Cardiac Fail 9:350–353

    Google Scholar 

  52. Kregel KC (2006) Resource book for the design of animal exercise protocols. American Physiological Society

  53. Kuznetsov AV, Smigelskaite J, Doblander C, Janakiraman M, Hermann M, Wurm M, Scheidl SF, Sucher R, Deutschmann A, Troppmair J (2008) Survival signaling by C-RAF: mitochondrial reactive oxygen species and Ca2+ are critical targets. Mol Biol Cell 28:2304–2313. doi:10.1128/MCB.00683-07

    CAS  Google Scholar 

  54. Langley SR, Dwyer J, Drozdov I, Yin X, Mayr M (2013) Proteomics: from single molecules to biological pathways. Cardiovasc Res 97:612–622. doi:10.1093/cvr/cvs346

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Lerchenmuller C, Rosenzweig A (2014) Mechanisms of exercise-induced cardiac growth. Drug Discov Today. doi:10.1016/j.drudis.2014.03.010

    PubMed  Google Scholar 

  56. Li C, Qiu Q, Wang Y, Li P, Xiao C, Wang H, Lin Y, Wang W (2014) Time course label-free quantitative analysis of cardiac muscles of rats after myocardial infarction. Mol BioSyst 10:505–513. doi:10.1039/c3mb70422j

    CAS  PubMed  Google Scholar 

  57. Liebler DC, Zimmerman LJ (2013) Targeted quantitation of proteins by mass spectrometry. Biochemistry 52:3797–3806. doi:10.1021/bi400110b

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Liu Y, Huttenhain R, Collins B, Aebersold R (2013) Mass spectrometric protein maps for biomarker discovery and clinical research. Expert Rev Mol Diagn 13:811–825. doi:10.1586/14737159.2013.845089

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Lotia S, Montojo J, Dong Y, Bader GD, Pico AR (2013) Cytoscape app store. Bioinformatics 29:1350–1351. doi:10.1093/bioinformatics/btt138

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Ma Y, de Castro Bras LE, Toba H, Iyer RP, Hall ME, Winniford MD, Lange RA, Tyagi SC, Lindsey ML (2014) Myofibroblasts and the extracellular matrix network in post-myocardial infarction cardiac remodeling. Pflug Archiv 466:1113–1127. doi:10.1007/s00424-014-1463-9

    CAS  Google Scholar 

  61. Ma Y, Halade GV, Lindsey ML (2012) Extracellular matrix and fibroblast communication following myocardial infarction. J Cardiovasc Transl Res 5:848–857. doi:10.1007/s12265-012-9398-z

    PubMed Central  PubMed  Google Scholar 

  62. Matros A, Kaspar S, Witzel K, Mock HP (2011) Recent progress in liquid chromatography-based separation and label-free quantitative plant proteomics. Phytochemistry 72:963–974. doi:10.1016/j.phytochem.2010.11.009

    CAS  PubMed  Google Scholar 

  63. Megger DA, Bracht T, Meyer HE, Sitek B (2013) Label-free quantification in clinical proteomics. Biochim Biophys Acta. doi:10.1016/j.bbapap.2013.04.001

    Google Scholar 

  64. Min CK, Yeom DR, Lee KE, Kwon HK, Kang M, Kim YS, Park ZY, Jeon H, Kim do H (2012) Coupling of ryanodine receptor 2 and voltage-dependent anion channel 2 is essential for Ca(2)+ transfer from the sarcoplasmic reticulum to the mitochondria in the heart. Biochem J 447:371–379. doi:10.1042/BJ20120705

    CAS  PubMed  Google Scholar 

  65. Moreira-Gonçalves D, Henriques-Coelho T, Fonseca H, Ferreira RM, Amado F, Leite-Moreira A, Duarte JA (2011) Moderate exercise training provides left ventricular tolerance to acute pressure overload. Am J Physiol Heart Circ Physiol 300:H1044–H1052. doi:10.1152/ajpheart.01008.2010

    PubMed  Google Scholar 

  66. Nahnsen S, Bielow C, Reinert K, Kohlbacher O (2013) Tools for label-free peptide quantification. Mol Cell Proteomics 12:549–556. doi:10.1074/mcp.R112.025163

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Nam H, Wang CY, Zhang L, Zhang W, Hojyo S, Fukada T, Knutson MD (2013) ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders. Haematologica 98:1049–1057. doi:10.3324/haematol.2012.072314

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A et al (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. doi:10.1016/S0140-6736(14)60460-8

    Google Scholar 

  69. Nguyen NT, Zhang X, Wu C, Lange RA, Chilton RJ, Lindsey ML, Jin YF (2014) Integrative computational and experimental approaches to establish a post-myocardial infarction knowledge map. PLoS Comput Biol 10:e1003472. doi:10.1371/journal.pcbi.1003472

    PubMed Central  PubMed  Google Scholar 

  70. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250:4007–4021

    PubMed Central  PubMed  Google Scholar 

  71. Padrão AI, Ferreira RMP, Vitorino R, Alves RMP, Neuparth MJ, Duarte JA, Amado F (2011) OXPHOS susceptibility to oxidative modifications: the role of heart mitochondrial subcellular location. Biochim Biophys Acta 1807:1106–1113. doi:10.1016/j.bbabio.2011.04.002

    PubMed  Google Scholar 

  72. Paul D, Kumar A, Gajbhiye A, Santra MK, Srikanth R (2013) Mass spectrometry-based proteomics in molecular diagnostics: discovery of cancer biomarkers using tissue culture. Biomed Res Int 2013:783131. doi:10.1155/2013/783131

    PubMed Central  PubMed  Google Scholar 

  73. Perrino C, Gargiulo G, Pironti G, Franzone A, Scudiero L, De Laurentis M, Magliulo F, Ilardi F, Carotenuto G, Schiattarella GG, Esposito G (2011) Cardiovascular effects of treadmill exercise in physiological and pathological preclinical settings. Am J Physiol Heart Circ Physiol 300:H1983–H1989. doi:10.1152/ajpheart.00784.2010

    CAS  PubMed  Google Scholar 

  74. Petriz BA, Cunha VN, Villeth GR, Mehta A, Rocha LA, Silva ON, Almeida JA, Morais PK, Simoes HG, Franco OL (2013) Effects of acute exercise over heart proteome from monogenic obese (ob/ob) mice. J Cell Physiol 228:824–834. doi:10.1002/jcp.24231

    CAS  PubMed  Google Scholar 

  75. Piersma SR, Warmoes MO, de Wit M, de Reus I, Knol JC, Jimenez CR (2013) Whole gel processing procedure for GeLC–MS/MS based proteomics. Proteome Sci 11:17. doi:10.1186/1477-5956-11-17

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Pons S, Martin V, Portal L, Zini R, Morin D, Berdeaux A, Ghaleh B (2013) Regular treadmill exercise restores cardioprotective signaling pathways in obese mice independently from improvement in associated co-morbidities. J Mol Cell Cardiol 54:82–89. doi:10.1016/j.yjmcc.2012.11.010

    CAS  PubMed  Google Scholar 

  77. Powers SK, Quindry JC, Kavazis AN (2008) Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury. Free Radic Biol Med 44:193–201. doi:10.1016/j.freeradbiomed.2007.02.006

    CAS  PubMed  Google Scholar 

  78. Powers SK, Sollanek KJ, Wiggs MP, Demirel HA, Smuder AJ (2014) Exercise-induced improvements in myocardial antioxidant capacity: the antioxidant players and cardioprotection. Free Radic Res 48:43–51. doi:10.3109/10715762.2013.825371

    CAS  PubMed  Google Scholar 

  79. Rabilloud T, Chevallet M, Luche S, Lelong C (2010) Two-dimensional gel electrophoresis in proteomics: past, present and future. J Proteomics 73:2064–2077. doi:10.1016/j.jprot.2010.05.016

    CAS  PubMed  Google Scholar 

  80. Ranek MJ, Terpstra EJ, Li J, Kass DA, Wang X (2013) Protein kinase g positively regulates proteasome-mediated degradation of misfolded proteins. Circulation 128:365–376. doi:10.1161/CIRCULATIONAHA.113.001971

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Sridhar R, Ramakrishna S (2013) Expression of cardiac proteins in neonatal cardiomyocytes on PGS/fibrinogen core/shell substrate for Cardiac tissue engineering. Int J Cardiol 167:1461–1468. doi:10.1016/j.ijcard.2012.04.045

    PubMed  Google Scholar 

  82. Rocha LA, Petriz BA, Borges DH, Oliveira RJ, de Andrade RV, Domont GB, Pereira RW, Franco OL (2012) High molecular mass proteomics analyses of left ventricle from rats subjected to differential swimming training. BMC physiol 12:11. doi:10.1186/1472-6793-12-11

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Roof SR, Tang L, Ostler JE, Periasamy M, Gyorke S, Billman GE, Ziolo MT (2013) Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise. Basic Res Cardiol 108:332. doi:10.1007/s00395-013-0332-6

    PubMed Central  PubMed  Google Scholar 

  84. Rose BA, Force T, Wang Y (2010) Mitogen-activated protein kinase signaling in the heart: angels versus demons in a heart-breaking tale. Physiol Rev 90:1507–1546. doi:10.1152/physrev.00054.2009

    CAS  PubMed  Google Scholar 

  85. Rosenzweig A (2012) Medicine. Cardiac regeneration. Science 338:1549–1550. doi:10.1126/science.1228951

    PubMed  Google Scholar 

  86. Salem KA, Qureshi MA, Sydorenko V, Parekh K, Jayaprakash P, Iqbal T, Singh J, Oz M, Adrian TE, Howarth FC (2013) Effects of exercise training on excitation-contraction coupling and related mRNA expression in hearts of Goto-Kakizaki type 2 diabetic rats. Mol Cell Biochem 380:83–96. doi:10.1007/s11010-013-1662-2

    CAS  PubMed  Google Scholar 

  87. Silva A, Vitorino R, Domingues MR, Spickett CM, Domingues P (2013) Post-translational modifications and mass spectrometry detection. Free Radic Biol Med. doi:10.1016/j.freeradbiomed.2013.08.184

    Google Scholar 

  88. Sun B, Wang JH, Lv YY, Zhu SS, Yang J, Ma JZ (2008) Proteomic adaptation to chronic high intensity swimming training in the rat heart. Comp Biochem Physiol Part D Genomics Proteomics 3:108–117. doi:10.1016/j.cbd.2007.11.001

    PubMed  Google Scholar 

  89. Sun Z, Hamilton KL, Reardon KF (2012) Phosphoproteomics and molecular cardiology: techniques, applications and challenges. J Mol Cell Cardiol 53:354–368. doi:10.1016/j.yjmcc.2012.06.001

    CAS  PubMed  Google Scholar 

  90. Tannu NS, Hemby SE (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat Protoc 1:1732–1742. doi:10.1038/nprot.2006.256

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Tardiff JC (2006) Cardiac hypertrophy: stressing out the heart. J Clin Invest 116:1467–1470. doi:10.1172/JCI28884

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Thomas S, Bonchev D (2010) A survey of current software for network analysis in molecular biology. Hum Genomics 4:353–360

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Ullrich ND, Valdivia HH, Niggli E (2012) PKA phosphorylation of cardiac ryanodine receptor modulates SR luminal Ca2+ sensitivity. J Mol Cell Cardiol 53:33–42. doi:10.1016/j.yjmcc.2012.03.015

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Van Riper SK, de Jong EP, Carlis JV, Griffin TJ (2013) Mass spectrometry-based proteomics: basic principles and emerging technologies and directions. Adv Exp Med Biol 990:1–35. doi:10.1007/978-94-007-5896-4_1

    PubMed  Google Scholar 

  95. Vettor R, Valerio A, Ragni M, Trevellin E, Granzotto M, Olivieri M, Tedesco L, Ruocco C, Fossati A, Fabris R, Serra R, Carruba MO, Nisoli E (2014) Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism. Am J Physiol Endocrinol Metab 306:E519–E528. doi:10.1152/ajpendo.00617.2013

    CAS  PubMed  Google Scholar 

  96. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, Nadal-Ginard B, Torella D, Ellison GM (2012) The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J. doi:10.1093/eurheartj/ehs338

    PubMed Central  PubMed  Google Scholar 

  97. Whittaker P (1997) Collagen and ventricular remodeling after acute myocardial infarction: concepts and hypotheses. Basic Res Cardiol 92:79–81

    CAS  PubMed  Google Scholar 

  98. Wisloff U, Helgerud J, Kemi OJ, Ellingsen O (2001) Intensity-controlled treadmill running in rats: VO(2 max) and cardiac hypertrophy. Am J Physiol Heart Circ Physiol 280:H1301–H1310

    CAS  PubMed  Google Scholar 

  99. Wu Q, Yuan H, Zhang L, Zhang Y (2012) Recent advances on multidimensional liquid chromatography-mass spectrometry for proteomics: from qualitative to quantitative analysis—a review. Anal Chim Acta 731:1–10. doi:10.1016/j.aca.2012.04.010

    CAS  PubMed  Google Scholar 

  100. Xiang F, Shi Z, Guo X, Qiu Z, Chen X, Huang F, Sha J (2011) Proteomic analysis of myocardial tissue from the border zone during early stage post-infarct remodelling in rats. Eur J Heart Fail 13:254–263. doi:10.1093/eurjhf/hfq196

    CAS  PubMed  Google Scholar 

  101. Xu X, Zhao W, Wan W, Ji LL, Powers AS, Erikson JM, Zhang JQ (2010) Exercise training combined with angiotensin II receptor blockade reduces oxidative stress after myocardial infarction in rats. Exp Physiol 95:1008–1015. doi:10.1113/expphysiol.2010.054221

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Xue Y, Liu Z, Cao J, Ma Q, Gao X, Wang Q, Jin C, Zhou Y, Wen L, Ren J (2011) GPS 2.1: enhanced prediction of kinase-specific phosphorylation sites with an algorithm of motif length selection. Protein Eng Des Sel 24:255–260. doi:10.1093/protein/gzq094

    CAS  PubMed  Google Scholar 

  103. Yabluchanskiy A, Li Y, Chilton RJ, Lindsey ML (2013) Matrix metalloproteinases: drug targets for myocardial infarction. Curr Drug Targets 14:276–286

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Yates JR (2013) The revolution and evolution of shotgun proteomics for large-scale proteome analysis. J Am Chem Soc. doi:10.1021/ja3094313

    Google Scholar 

Download references

Acknowledgments

This work was supported by Portuguese Foundation for Science and Technology (FCT), European Union, QREN, FEDER and COMPETE for funding the QOPNA research unit (project PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296) and the research project (EXPL/DTP-DES/1010/2013; FCOMP-01-0124-FEDER-041115), RNEM (National Mass Spectrometry Network), Mais Centro-Programa Operacional Regional do Centro e União Europeia (CENTRO-07-ST24-FEDER-002030) and COST Action BM1307.

Author information

Authors and Affiliations

  1. Mass Spectrometry Group, QOPNA, Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal

    Rita Ferreira, Ana Lúcia Azevedo & Rui Vitorino

  2. CIAFEL, Faculty of Sports, University of Porto, Porto, Portugal

    Daniel Moreira-Gonçalves & José Alberto Duarte

  3. QOPNA, School of Health Sciences, University of Aveiro, Aveiro, Portugal

    Francisco Amado

  4. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal

    Daniel Moreira-Gonçalves

  5. Institute for Research in Biomedicine, iBiMED, Health Sciences Program, University of Aveiro, Aveiro, Portugal

    Rui Vitorino

Authors
  1. Rita Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Moreira-Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Lúcia Azevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. José Alberto Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francisco Amado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui Vitorino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rui Vitorino.

Electronic supplementary material

Below is the link to the electronic supplementary material.

395_2014_454_MOESM1_ESM.png

Figure S1: Protein network morphology visualizing the cross-talk of the protein targets of exercise training identified using gel-based and gel-free approaches. Protein network morphology was constructed using the Cytoscape platform. (PNG 562 kb)

Table S1: List of proteins modulated in heart by exercise training. (XLSX 28 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferreira, R., Moreira-Gonçalves, D., Azevedo, A.L. et al. Unraveling the exercise-related proteome signature in heart. Basic Res Cardiol 110, 454 (2015). https://doi.org/10.1007/s00395-014-0454-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-014-0454-5

Keywords

Search

Navigation