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Proteomics of Atherosclerosis

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Inflammation and Atherosclerosis

Abstract

The human genome contains 20,000 protein-encoding genes, which is similar to the genome of simple organisms, such as C. elegans. It is therefore the regulation of gene expression, the interaction of proteins and their post-translational modifications that define biological complexity. Besides, the genomes also contain gene duplications and non-expressed pseudogenes that can be responsible for interspecies differences and similarities. Unlike the genome, the proteome is dynamic: proteins are subjected to extensive post-translational modifications (PTMs), proteolysis, or compartimentalization. The ultimate goal of proteomics is to analyse the totality of proteins. The present chapter reviews the proteomic tools currently available and highlights achievements in the application of these advanced technologies to atherosclerosis.

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References

  1. Picotti P, Aebersold R, Domon B (2007) The implications of proteolytic background for shotgun proteomics. Mol Cell Proteomics 6(9):1589–1598

    Article  PubMed  CAS  Google Scholar 

  2. Patterson SD, Aebersold RH (2003) Proteomics: the first decade and beyond. Nat Genet 33(Suppl):311–323

    Article  PubMed  CAS  Google Scholar 

  3. Armirotti A, Damonte G (2010) Achievements and perspectives of top-down proteomics. Proteomics 10(20):3566–3576

    Article  PubMed  CAS  Google Scholar 

  4. O’Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250(10):4007–4021

    PubMed  Google Scholar 

  5. Washburn MP, Wolters D, Yates JR 3rd (2001) Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol 19(3):242–247

    Article  PubMed  CAS  Google Scholar 

  6. Domon B, Aebersold R (2006) Mass spectrometry and protein analysis. Science 312(5771):212–217

    Article  PubMed  CAS  Google Scholar 

  7. Unlu M, Morgan ME, Minden JS (1997) Difference gel electrophoresis: a single gel method for detecting changes in protein extracts. Electrophoresis 18(11):2071–2077

    Article  PubMed  CAS  Google Scholar 

  8. Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 17(10):994–999

    Article  PubMed  CAS  Google Scholar 

  9. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A et al (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386

    Article  PubMed  CAS  Google Scholar 

  10. Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S et al (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3(12):1154–1169

    Article  PubMed  CAS  Google Scholar 

  11. Dayon L, Hainard A, Licker V, Turck N, Kuhn K, Hochstrasser DF et al (2008) Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. Anal Chem 80(8):2921–2931

    Article  PubMed  CAS  Google Scholar 

  12. Zhu WH, Smith JW, Huang CM (2010) Mass spectrometry-based label-free quantitative proteomics. J Biomed Biotechnol 2010:840518

    PubMed  Google Scholar 

  13. Zybailov B, Coleman MK, Florens L, Washburn MP (2005) Correlation of relative abundance ratios derived from peptide ion chromatograms and spectrum counting for quantitative proteomic analysis using stable isotope labeling. Anal Chem 77(19):6218–6224

    Article  PubMed  CAS  Google Scholar 

  14. Wang WX, Zhou HH, Lin H, Roy S, Shaler TA, Hill LR et al (2003) Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards. Anal Chem 75(18):4818–4826

    Article  PubMed  CAS  Google Scholar 

  15. Schiess R, Wollscheid B, Aebersold R (2009) Targeted proteomic strategy for clinical biomarker discovery. Mol Oncol 3(1):33–44

    Article  PubMed  CAS  Google Scholar 

  16. Mayr M, Zhang J, Greene AS, Gutterman D, Perloff J, Ping P (2006) Proteomics-based development of biomarkers in cardiovascular disease: mechanistic, clinical, and therapeutic insights. Mol Cell Proteomics 5(10):1853–1864

    Article  PubMed  CAS  Google Scholar 

  17. Blanco-Colio LM, López JA, Martínez-Pinna Albar R, Egido J, Martín-Ventura JL (2009) Vascular proteomics, a translational approach: from traditional to novel proteomic techniques. Expert Rev Proteomic 6(5):461–464

    Article  CAS  Google Scholar 

  18. Mayr M, Mayr U, Chung Y-L, Yin X, Griffiths JR, Xu Q (2004) Vascular proteomics: linking proteomic and metabolomic changes. Proteomics 4(12):3751–3761

    Article  PubMed  CAS  Google Scholar 

  19. Arrell DK, Neverova I, Van Eyk JE (2001) Cardiovascular proteomics: evolution and potential. Circ Res 88(8):763–773

    Article  PubMed  CAS  Google Scholar 

  20. Martinez-Pinna R, Martin-Ventura JL, Mas S, Blanco-Colio LM, Tunon J, Egido J (2008) Proteomics in atherosclerosis. Curr Atheroscler Rep 10(3):209–215

    Article  PubMed  CAS  Google Scholar 

  21. Didangelos A, Simper D, Monaco C, Mayr M (2009) Proteomics of acute coronary syndromes. Curr Atheroscler Rep 11(3):188–195

    Article  PubMed  CAS  Google Scholar 

  22. Mayr M, Chung YL, Mayr U, Yin X, Ly L, Troy H et al (2005) Proteomic and metabolomic analyses of atherosclerotic vessels from apolipoprotein E-deficient mice reveal alterations in inflammation, oxidative stress, and energy metabolism. Arterioscler Thromb Vasc Biol 25(10):2135–2142

    Article  PubMed  CAS  Google Scholar 

  23. You S-A, Archacki SR, Angheloiu G, Moravec CS, Rao S, Kinter M et al (2003) Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis. Physiol Genomics 13(1):25–30

    PubMed  CAS  Google Scholar 

  24. Kiechl S, Willeit J, Egger G, Poewe W, Oberhollenzer F (1997) Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 96(10):3300–3307

    PubMed  CAS  Google Scholar 

  25. Kiechl S, Aichner F, Gerstenbrand F, Egger G, Mair A, Rungger G et al (1994) Body iron stores and presence of carotid atherosclerosis. Results from the Bruneck Study. Arterioscler Thromb 14(10):1625–1630

    Article  PubMed  CAS  Google Scholar 

  26. Duran MC, Mas S, Martin-Ventura JL, Meilhac O, Michel JB, Gallego-Delgado J et al (2003) Proteomic analysis of human vessels: application to atherosclerotic plaques. Proteomics 3(6):973–978

    Article  PubMed  CAS  Google Scholar 

  27. Martin-Ventura JL, Duran MC, Blanco-Colio LM, Meilhac O, Leclercq A, Michel JB et al (2004) Identification by a differential proteomic approach of heat shock protein 27 as a potential marker of atherosclerosis. Circulation 110(15):2216–2219

    Article  PubMed  CAS  Google Scholar 

  28. Martin-Ventura JL, Nicolas V, Houard X, Blanco-Colio LM, Leclercq A, Egido J et al (2006) Biological significance of decreased HSP27 in human atherosclerosis. Arterioscler Thromb Vasc Biol 26(6):1337–1343

    Article  PubMed  CAS  Google Scholar 

  29. Durán MC, Martín-Ventura JL, Mohammed S, Barderas MG, Blanco-Colio LM, Mas S et al (2007) Atorvastatin modulates the profile of proteins released by human atherosclerotic plaques. Eur J Pharmacol 562(1–2):119–129

    Article  PubMed  Google Scholar 

  30. Lepedda AJ, Cigliano A, Cherchi GM, Spirito R, Maggioni M, Carta F et al (2009) A proteomic approach to differentiate histologically classified stable and unstable plaques from human carotid arteries. Atherosclerosis 203(1):112–118

    Article  PubMed  CAS  Google Scholar 

  31. Bagnato C, Thumar J, Mayya V, Hwang S-I, Zebroski H, Claffey KP et al (2007) Proteomics analysis of human coronary atherosclerotic plaque: a feasibility study of direct tissue proteomics by liquid chromatography and tandem mass spectrometry. Mol Cell Proteomics 6(6):1088–1102

    Article  PubMed  CAS  Google Scholar 

  32. Katsuda S, Kaji T (2003) Atherosclerosis and extracellular matrix. J Atheroscler Thromb 10(5):267–274

    Article  PubMed  CAS  Google Scholar 

  33. Didangelos A, Yin X, Mandal K, Baumert M, Jahangiri M, Mayr M (2010) Proteomics characterization of extracellular space components in the human aorta. Mol Cell Proteomics 9(9):2048–2062

    Article  PubMed  CAS  Google Scholar 

  34. Talusan P, Bedri S, Yang S, Kattapuram T, Silva N, Roughley PJ et al (2005) Analysis of intimal proteoglycans in atherosclerosis-prone and atherosclerosis-resistant human arteries by mass spectrometry. Mol Cell Proteomics 4(9):1350–1357

    Article  PubMed  CAS  Google Scholar 

  35. Ross MD, Bruggeman LA, Hanss B, Sunamoto M, Marras D, Klotman ME et al (2003) Podocan, a novel small leucine-rich repeat protein expressed in the sclerotic glomerular lesion of experimental HIV-associated nephropathy. J Biol Chem 278(35):33248–33255

    Article  PubMed  CAS  Google Scholar 

  36. Sutherland MK, Geoghegan JC, Yu CP, Turcott E, Skonier JE, Winkler DG et al (2004) Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation. Bone 35(4):828–835

    Article  PubMed  CAS  Google Scholar 

  37. Ngo ST, Noakes PG, Phillips WD (2007) Neural agrin: a synaptic stabiliser. Int J Biochem Cell Biol 39(5):863–867

    Article  PubMed  CAS  Google Scholar 

  38. Bruneel A, Labas V, Mailloux A, Sharma S, Vinh J, Vaubourdolle M et al (2003) Proteomic study of human umbilical vein endothelial cells in culture. Proteomics 3(5):714–723

    Article  PubMed  CAS  Google Scholar 

  39. McGregor E, Kempster L, Wait R, Welson S, Gosling M, Dunn M et al (2001) Identification and mapping of human saphenous vein medial smooth muscle proteins by two-dimensional polyacrylamide gel electrophoresis. Proteomics 1(11):1405–1414

    Article  PubMed  CAS  Google Scholar 

  40. Dupont A, Corseaux D, Dekeyzer O, Drobecq H, Guihot A, Susen S et al (2005) The proteome and secretome of human arterial smooth muscle cells. Proteomics 5(2):585–596

    Article  PubMed  CAS  Google Scholar 

  41. Mayr U, Mayr M, Yin X, Begum S, Tarelli E, Wait R et al (2005) Proteomic dataset of mouse aortic smooth muscle cells. Proteomics 5(17):4546–4557

    Article  PubMed  CAS  Google Scholar 

  42. Tunica DG, Yin X, Sidibe A, Stegemann C, Nissum M, Zeng L et al (2009) Proteomic analysis of the secretome of human umbilical vein endothelial cells using a combination of free-flow electrophoresis and nanoflow LC-MS/MS. Proteomics 9(21):4991–4996

    Article  PubMed  CAS  Google Scholar 

  43. Burghoff S, Schrader J (2011) Secretome of human endothelial cells under shear stress. J Proteome Res 10(3):1160–1169

    Article  PubMed  CAS  Google Scholar 

  44. Pellieux C, Desgeorges A, Pigeon C, Chambaz C, Yin H, Hayoz D et al (2003) Cap G, a gelsolin family protein modulating protective effects of unidirectional shear stress. J Biol Chem 278(31):29136–29144

    Article  PubMed  CAS  Google Scholar 

  45. McGregor E, Kempster L, Wait R, Gosling M, Dunn M, Powell J (2004) F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress - A proteomic approach. Mol Cell Proteomics 3(2):115–124

    PubMed  CAS  Google Scholar 

  46. Patton WF, Erdjument-Bromage H, Marks AR, Tempst P, Taubman MB (1995) Components of the protein synthesis and folding machinery are induced in vascular smooth muscle cells by hypertrophic and hyperplastic agents. Identification by comparative protein phenotyping and microsequencing. J Biol Chem 270(36):21404–21410

    Article  PubMed  CAS  Google Scholar 

  47. Boccardi C, Cecchettini A, Caselli A, Camici G, Evangelista M, Mercatanti A et al (2007) A proteomic approach to the investigation of early events involved in the activation of vascular smooth muscle cells. Cell Tissue Res 329(1):119–128

    Article  PubMed  CAS  Google Scholar 

  48. Ross R (1999) Atherosclerosis is an inflammatory disease. Am Heart J 138(5 Pt 2):S419–S420

    Article  PubMed  CAS  Google Scholar 

  49. Jang WG, Kim HS, Park KG, Park YB, Yoon KH, Han SW et al (2004) Analysis of proteome and transcriptome of tumor necrosis factor alpha stimulated vascular smooth muscle cells with or without alpha lipoic acid. Proteomics 4(11):3383–3393

    Article  PubMed  CAS  Google Scholar 

  50. Verhoeckx K, Bijlsma S, de Groene E, Witkamp R, van der Greef J, Rodenburg R (2004) A combination of proteomics, principal component analysis and transcriptomics is a powerful tool for the identification of biomarkers for macrophage maturation in the U937 cell line. Proteomics 4(4):1014–1028

    Article  PubMed  CAS  Google Scholar 

  51. Simper D, Stalboerger PG, Panetta CJ, Wang S, Caplice NM (2002) Smooth muscle progenitor cells in human blood. Circulation 106(10):1199–1204

    Article  PubMed  CAS  Google Scholar 

  52. Hristov M, Zernecke A, Schober A, Weber C (2008) Adult progenitor cells in vascular remodeling during atherosclerosis. Biol Chem 389(7):837–844

    Article  PubMed  CAS  Google Scholar 

  53. Prokopi M, Pula G, Mayr U, Devue C, Gallagher J, Xiao Q et al (2009) Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures. Blood 114(3):723–732

    PubMed  CAS  Google Scholar 

  54. Urbich C, De Souza AI, Rossig L, Yin X, Xing Q, Prokopi M et al (2011) Proteomic characterization of human early pro-angiogenic cells. J Mol Cell Cardiol 50(2):333–336

    Article  PubMed  CAS  Google Scholar 

  55. Richardson MR, Yoder MC (2011) Endothelial progenitor cells: quo vadis? J Mol Cell Cardiol 50(2):266–272

    Article  PubMed  CAS  Google Scholar 

  56. Urbich C, Aicher A, Heeschen C, Dernbach E, Hofmann WK, Zeiher AM et al (2005) Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J Mol Cell Cardiol 39(5):733–742

    Article  PubMed  CAS  Google Scholar 

  57. Pula G, Mayr U, Evans C, Prokopi M, Vara DS, Yin X et al (2009) Proteomics identifies thymidine phosphorylase as a key regulator of the angiogenic potential of colony-forming units and endothelial progenitor cell cultures. Circ Res 104(1):32–40

    Article  PubMed  CAS  Google Scholar 

  58. Zoll J, Fontaine V, Gourdy P, Barateau V, Vilar J, Leroyer A et al (2008) Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition. Cardiovasc Res 77(3):471–480

    Article  PubMed  CAS  Google Scholar 

  59. Simper D, Mayr U, Urbich C, Zampetaki A, Prokopi M, Didangelos A et al (2010) Comparative proteomics profiling reveals role of smooth muscle progenitors in extracellular matrix production. Arterioscler Throm Vasc Biol 30(7):1325–1332

    Article  CAS  Google Scholar 

  60. Hu Y, Zhang Z, Torsney E, Afzal AR, Davison F, Metzler B et al (2004) Abundant progenitor cells in the adventitia contribute to atherosclerosis of vein grafts in ApoE-deficient mice. J Clin Invest 113(9):1258–1265

    PubMed  CAS  Google Scholar 

  61. Yin X, Mayr M, Xiao Q, Mayr U, Tarelli E, Wait R et al (2005) Proteomic dataset of Sca-1+ progenitor cells. Proteomics 5(17):4533–4545

    Article  PubMed  CAS  Google Scholar 

  62. Yin X, Mayr M, Xiao Q, Wang W, Xu Q (2006) Proteomic analysis reveals higher demand for antioxidant protection in embryonic stem cell-derived smooth muscle cells. Proteomics 6(24):6437–6446

    Article  PubMed  CAS  Google Scholar 

  63. Mayr M, Zampetaki A, Sidibe A, Mayr U, Yin X, De Souza AI et al (2008) Proteomic and metabolomic analysis of smooth muscle cells derived from the arterial media and adventitial progenitors of apolipoprotein E-deficient mice. Circ Res 102(9):1046–1056

    Article  PubMed  CAS  Google Scholar 

  64. Rifai N, Gillette MA, Carr SA (2006) Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24(8):971–983

    Article  PubMed  CAS  Google Scholar 

  65. Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1(11):845–867

    Article  PubMed  CAS  Google Scholar 

  66. Bjorhall K, Miliotis T, Davidsson P (2005) Comparison of different depletion strategies for improved resolution in proteomic analysis of human serum samples. Proteomics 5(1):307–317

    Article  PubMed  Google Scholar 

  67. Wilson AM, Kimura E, Harada RK, Nair N, Narasimhan B, Meng XY et al (2007) Beta2-microglobulin as a biomarker in peripheral arterial disease: proteomic profiling and clinical studies. Circulation 116(12):1396–1403

    Article  PubMed  CAS  Google Scholar 

  68. Mateos-Caceres PJ, Garcia-Mendez A, Lopez Farre A, Macaya C, Nunez A, Gomez J et al (2004) Proteomic analysis of plasma from patients during an acute coronary syndrome. J Am Coll Cardiol 44(8):1578–1583

    Article  PubMed  CAS  Google Scholar 

  69. Gerszten RE, Carr SA, Sabatine M (2010) Integration of proteomic-based tools for improved biomarkers of myocardial injury. Clin Chem 56(2):194–201

    Article  PubMed  CAS  Google Scholar 

  70. Edwards AV, White MY, Cordwell SJ (2008) The role of proteomics in clinical cardiovascular biomarker discovery. Mol Cell Proteomics 7(10):1824–1837

    Article  PubMed  CAS  Google Scholar 

  71. de Kleijn DP, Moll FL, Hellings WE, Ozsarlak-Sozer G, de Bruin P, Doevendans PA et al (2010) Local atherosclerotic plaques are a source of prognostic biomarkers for adverse cardiovascular events. Arterioscler Thromb Vasc Biol 30(3):612–619

    Article  PubMed  Google Scholar 

  72. Mayr M, Madhu B, Xu Q (2007) Proteomics and metabolomics combined in cardiovascular research. Trends Cardiovasc Med 17(2):43–48

    Article  PubMed  CAS  Google Scholar 

  73. Mayr M, Mayr U, Chung YL, Yin X, Griffiths JR, Xu Q (2004) Vascular proteomics: linking proteomic and metabolomic changes. Proteomics 4(12):3751–3761

    Article  PubMed  CAS  Google Scholar 

  74. Mayr M, May D, Oren G, Madhu B, Gilon D, Yin X et al (2011) Metabolic homeostasis is maintained in myocardial hibernation by adaptive changes in the transcriptome and proteome. J Mol Cell Cardiol 50(6):982–990

    Article  PubMed  CAS  Google Scholar 

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Abonnenc, M., Mayr, M. (2012). Proteomics of Atherosclerosis. In: Wick, G., Grundtman, C. (eds) Inflammation and Atherosclerosis. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0338-8_13

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