The effect of disease on human cardiac protein expression profiles in paired samples from right and left ventricles

Clinical Proteomics

M-Saadeh Suleiman²  Gianni D Angelini²  Kate Heesom¹  Ben Littlejohns² 

[1] Proteomics Facility, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol, UK;Bristol Heart Institute, School of Clinical Sciences, Faculty of Medicine & Dentistry, University of Bristol, Bristol, UK

关键词: Mass spectrometry;    TMT tag;    Ventricular biopsies;    Aortic valve stenosis;    Coronary artery disease;    Cardiac;    Human;    Proteomics;   

Others  :  1092829
DOI  :  10.1186/1559-0275-11-34

 received in 2014-04-25, accepted in 2014-07-28,  发布年份 2014

【 摘 要 】

Background

Cardiac diseases (e.g. coronary and valve) are associated with ventricular cellular remodeling. However, ventricular biopsies from left and right ventricles from patients with different pathologies are rare and thus little is known about disease-induced cellular remodeling in both sides of the heart and between different diseases. We hypothesized that the protein expression profiles between right and left ventricles of patients with aortic valve stenosis (AVS) and patients with coronary artery disease (CAD) are different and that the protein profile is different between the two diseases. Left and right ventricular biopsies were collected from patients with either CAD or AVS. The biopsies were processed for proteomic analysis using isobaric tandem mass tagging and analyzed by reverse phase nano-LC-MS/MS. Western blot for selected proteins showed strong correlation with proteomic analysis.

Results

Proteomic analysis between ventricles of the same disease (intra-disease) and between ventricles of different diseases (inter-disease) identified more than 500 proteins detected in all relevant ventricular biopsies. Comparison between ventricles and disease state was focused on proteins with relatively high fold (±1.2 fold difference) and significant (P < 0.05) differences. Intra-disease protein expression differences between left and right ventricles were largely structural for AVS patients and largely signaling/metabolism for CAD. Proteins commonly associated with hypertrophy were also different in the AVS group but with lower fold difference. Inter-disease differences between left ventricles of AVS and CAD were detected in 9 proteins. However, inter-disease differences between the right ventricles of CAD and AVS patients were associated with differences in 73 proteins. The majority of proteins which had a significant difference in one ventricle compared to the other pathology also had a similar trend in the adjacent ventricle.

Conclusions

This work demonstrates for the first time that left and right ventricles have a different proteome and that the difference is dependent on the type of disease. Inter-disease differential expression was more prominent for right ventricles. The finding that a protein change in one ventricle was often associated with a similar trend in the adjacent ventricle for a large number of proteins suggests cross-talk proteome remodeling between adjacent ventricles.

【 授权许可】

   
2014 Littlejohns et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Chase A, Jackson CL, Angelini GL, Suleiman MS: Coronary artery disease progression is associated with increased resistance of hearts and myocytes to cardiac insults. Crit Care Med 2007, 35(10):2344-2351.
• [2]Ellinghaus P, Scheubel RJ, Dobrev D, Ravens U, Holtz J, Huetter J, Nielsch U, Morawietz H: Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays. J Thorac Cardiovasc Surg 2005, 129(6):1383-1390.
• [3]Kaab S, Barth AS, Margerie D, Dugas M, Gebauer M, Zwermann L, Merk S, Pfeufer A, Steinmeyer K, Bleich M, Kreuzer E, Steinbeck G, Nabauer M: Global gene expression in human myocardium-oligonucleotide microarray analysis of regional diversity and transcriptional regulation in heart failure. J Mol Med 2004, 82(5):308-316.
• [4]Barth AS, Merk S, Arnoldi E, Zwermann L, Kloos P, Gebauer M, Steinmeyer K, Bleich M, Kaab S, Hinterseer M, Kartmann H, Kreuzer E, Dugas M, Steinbeck G, Nabauer M: Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature. Circ Res 2005, 96(9):1022-1029.
• [5]Barth AS, Merk S, Arnoldi E, Zwermann L, Kloos P, Gebauer M, Steinmeyer K, Bleich M, Kaab S, Pfeufer A, Uberfuhr P, Dugas M, Steinbeck G, Nabauer M: Functional profiling of human atrial and ventricular gene expression. Pflugers Arch 2005, 450(4):201-208.
• [6]Asp J, Synnergren J, Jonsson M, Dellgren G, Jeppsson A: Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo. Physiol Genomics 2012, 44(1):89-98.
• [7]Borchert B, Tripathi S, Francino A, Navarro-Lopez F, Kraft T: The left and right ventricle of a patient with a R723G mutation of the beta-myosin heavy chain and severe hypertrophic cardiomyopathy show no differences in the expression of myosin mRNA. Cardiol J 2010, 17(5):518-522.
• [8]Periasamy M, Bhupathy P, Babu GJ: Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology. Cardiovasc Res 2008, 77(2):265-273.
• [9]Ashrafian H, McKenna WJ, Watkins H: Disease pathways and novel therapeutic targets in hypertrophic cardiomyopathy. Circ Res 2011, 109(1):86-96.
• [10]Oakley CE, Hambly BD, Curmi PM, Brown LJ: Myosin binding protein C: structural abnormalities in familial hypertrophic cardiomyopathy. Cell Res 2004, 14(2):95-110.
• [11]Flashman E, Redwood C, Moolman-Smook J, Watkins H: Cardiac myosin binding protein C: its role in physiology and disease. Circ Res 2004, 94(10):1279-1289.
• [12]Baba H, Ishiwata T, Takashi E, Xu G, Asano G: Expression and localization of lumican in the ischemic and reperfused rat heart. Jpn Circ J 2001, 65(5):445-450.
• [13]Engebretsen KV, Waehre A, Bjornstad JL, Skrbic B, Sjaastad I, Behmen D, Marstein HS, Yndestad A, Aukrust P, Christensen G, Tonnessen T: Decorin, lumican, and their GAG chain-synthesizing enzymes are regulated in myocardial remodeling and reverse remodeling in the mouse. J Appl Physiol (1985) 2013, 114(8):988-997.
• [14]Hwang JJ, Allen PD, Tseng GC, Lam CW, Fananapazir L, Dzau VJ, Liew CC: Microarray gene expression profiles in dilated and hypertrophic cardiomyopathic end-stage heart failure. Physiol Genomics 2002, 10(1):31-44.
• [15]Bergquist J, Baykut G, Bergquist M, Witt M, Mayer FJ, Baykut D: Human myocardial protein pattern reveals cardiac diseases. Int J Genom Proteonomics 2012, 2012:342659.
• [16]Di Somma S, Marotta M, Salvatore G, Cudemo G, Cuda G, De Vivo F, Di Benedetto MP, Ciaramella F, Caputo G, de Divitiis O: Changes in myocardial cytoskeletal intermediate filaments and myocyte contractile dysfunction in dilated cardiomyopathy: an in vivo study in humans. Heart 2000, 84(6):659-667.
• [17]Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B, Bauer E, Klovekorn WP, Schlepper M, Schaper W, Schaper J: Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium. Circ Res 2000, 86(8):846-853.
• [18]Iwai N, Shimoike H, Kinoshita M: Genes up-regulated in hypertrophied ventricle. Biochem Biophys Res Commun 1995, 209(2):527-534.
• [19]Schaper J, Froede R, Hein S, Buck A, Hashizume H, Speiser B, Friedl A, Bleese N: Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy. Circulation 1991, 83(2):504-514.
• [20]Fujita M, Mitsuhashi H, Isogai S, Nakata T, Kawakami A, Nonaka I, Noguchi S, Hayashi YK, Nishino I, Kudo A: Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro. Dev Biol 2012, 361(1):79-89.
• [21]Kong SW, Hu YW, Ho JW, Ikeda S, Polster S, John R, Hall JL, Bisping E, Pieske B, dos Remedios CG, Pu WT: Heart failure-associated changes in RNA splicing of sarcomere genes. Circ Cardiovasc Genet 2010, 3(2):138-146.
• [22]Birks EJ, Hall JL, Barton PJ, Grindle S, Latif N, Hardy JP, Rider JE, Banner NR, Khaghani A, Miller LW, Yacoub MH: Gene profiling changes in cytoskeletal proteins during clinical recovery after left ventricular-assist device support. Circulation 2005, 112(9 Suppl):I57-I64.
• [23]Nishida K, Yamaguchi O, Hirotani S, Hikoso S, Higuchi Y, Watanabe T, Takeda T, Osuka S, Morita T, Kondoh G, Uno Y, Kashiwase K, Taniike M, Nakai A, Matsumura Y, Miyazaki J, Sudo T, Hongo K, Kusakari Y, Kurihara S, Chien KR, Takeda J, Hori M, Otsu K: p38alpha mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure overload. Mol Cell Biol 2004, 24(24):10611-10620.
• [24]Muchir A, Wu W, Choi JC, Iwata S, Morrow J, Homma S, Worman HJ: Abnormal p38alpha mitogen-activated protein kinase signaling in dilated cardiomyopathy caused by lamin A/C gene mutation. Hum Mol Genet 2012, 21(19):4325-4333.
• [25]Schelbert HR: Anatomy and physiology of coronary blood flow. J Nucl Cardiol 2010, 17(4):545-554.
• [26]Cheng XW, Shi GP, Kuzuya M, Sasaki T, Okumura K, Murohara T: Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication. Circulation 2012, 125(12):1551-1562.
• [27]Liu A, Gao X, Zhang Q, Cui L: Cathepsin B inhibition attenuates cardiac dysfunction and remodeling following myocardial infarction by inhibiting the NLRP3 pathway. Mol Med Rep 2013, 8(2):361-366.
• [28]Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP: Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol 2004, 24(8):1359-1366.
• [29]Lin KM, Lin B, Lian IY, Mestril R, Scheffler IE, Dillmann WH: Combined and individual mitochondrial HSP60 and HSP10 expression in cardiac myocytes protects mitochondrial function and prevents apoptotic cell deaths induced by simulated ischemia-reoxygenation. Circulation 2001, 103(13):1787-1792.
• [30]Kapoor N, Gupta R, Menon ST, Folta-Stogniew E, Raleigh DP, Sakmar TP: Nucleobindin 1 is a calcium-regulated guanine nucleotide dissociation inhibitor of G{alpha}i1. J Biol Chem 2010, 285(41):31647-31660.
• [31]Valencia CA, Cotten SW, Duan J, Liu R: Modulation of nucleobindin-1 and nucleobindin-2 by caspases. FEBS Lett 2008, 582(2):286-290.
• [32]de Alba E, Tjandra N: Structural studies on the Ca2 + −binding domain of human nucleobindin (calnuc). Biochemistry 2004, 43(31):10039-10049.
• [33]Lin P, Yao Y, Hofmeister R, Tsien RY, Farquhar MG: Overexpression of CALNUC (nucleobindin) increases agonist and thapsigargin releasable Ca2+ storage in the Golgi. J Cell Biol 1999, 145(2):279-289.
• [34]Suleiman MS, Caputo M, Ascione R, Bryan AJ, Lucchetti V, Gomes WJ, Angelini GD: Metabolic differences between hearts of patients with aortic valve disease and hearts of patients with ischaemic disease. J Mol Cell Cardiol 1998, 30(11):2519-2523.
• [35]Allard MF, Henning SL, Wambolt RB, Granleese SR, English DR, Lopaschuk GD: Glycogen metabolism in the aerobic hypertrophied rat heart. Circulation 1997, 96(2):676-682.
• [36]Panguluri SK, Tur J, Fukumoto J, Deng W, Sneed KB, Kolliputi N, Bennett ES, Tipparaju SM: Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle. Am J Physiol Heart Circ Physiol 2013, 304(12):H1651-H1661.
• [37]Mao W, You T, Ye B, Li X, Dong HH, Hill JA, Li F, Xu H: Reactive oxygen species suppress cardiac NaV1.5 expression through Foxo1. PLoS One 2012, 7(2):e32738.
• [38]Letto J, Brosnan JT, Brosnan ME: Oxidation of 2-oxoisocaproate and 2-oxoisovalerate by the perfused rat heart. Interactions with fatty acid oxidation. Biochem Cell Biol 1990, 68(1):260-265.
• [39]Tskhovrebova L, Trinick J: Making muscle elastic: the structural basis of myomesin stretching. PLoS Biol 2012, 10(2):e1001264.
• [40]Siegert R, Perrot A, Keller S, Behlke J, Michalewska-Wludarczyk A, Wycisk A, Tendera M, Morano I, Ozcelik C: A myomesin mutation associated with hypertrophic cardiomyopathy deteriorates dimerisation properties. Biochem Biophys Res Commun 2011, 405(3):473-479.
• [41]Wetzelberger K, Baba SP, Thirunavukkarasu M, Ho YS, Maulik N, Barski OA, Conklin DJ, Bhatnagar A: Postischemic deactivation of cardiac aldose reductase: role of glutathione S-transferase P and glutaredoxin in regeneration of reduced thiols from sulfenic acids. J Biol Chem 2010, 285(34):26135-26148.
• [42]Yanagawa B, Algarni KD, Singh SK, Deb S, Vincent J, Elituv R, Desai ND, Rajamani K, McManus BM, Liu PP, Cohen EA, Radhakrishnan S, Dubbin JD, Schwartz L, Fremes SE: Clinical, biochemical, and genetic predictors of coronary artery bypass graft failure. J Thorac Cardiovasc Surg 2014, 148(2):515-520.
• [43]Sano A, Hineno T, Mizuno T, Kondoh K, Ueno S, Kakimoto Y, Inui K: Sphingolipid hydrolase activator proteins and their precursors. Biochem Biophys Res Commun 1989, 165(3):1191-1197.
• [44]Chen Q, Jin M, Zhu J, Xiao Q, Zhang L: Functions of heterogeneous nuclear ribonucleoproteins in stem cell potency and differentiation. BioMed Res Int 2013, 2013:623978.
• [45]Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y: Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature 1999, 401(6749):168-173.
• [46]Nascimben L, Ingwall JS, Lorell BH, Pinz I, Schultz V, Tornheim K, Tian R: Mechanisms for increased glycolysis in the hypertrophied rat heart. Hypertension 2004, 44(5):662-667.
• [47]Villeneuve C, Guilbeau-Frugier C, Sicard P, Lairez O, Ordener C, Duparc T, De Paulis D, Couderc B, Spreux-Varoquaux O, Tortosa F, Garnier A, Knauf C, Valet P, Borchi E, Nediani C, Gharib A, Ovize M, Delisle MB, Parini A, Mialet-Perez J: p53-PGC-1alpha pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced by monoamine oxidase-A upregulation: role in chronic left ventricular dysfunction in mice. Antioxid Redox Signal 2013, 18(1):5-18.
• [48]Beltrao P, Bork P, Krogan NJ, van Noort V: Evolution and functional cross-talk of protein post-translational modifications. Mol Syst Biol 2013, 9:714.
• [49]Cerny M, Skalak J, Cerna H, Brzobohaty B: Advances in purification and separation of posttranslationally modified proteins. J Proteomics 2013, 92:2-27.
• [50]Abdul-Ghani S, Heesom KJ, Angelini GD, Suleiman M-S: Cardiac Phosphoproteomics during Remote Ischemic Preconditioning: A Role for the Sarcomeric Z-Disk Proteins. BioMed Res Int 2014, 2014:11.
• [51]Oberg AL, Mahoney DW: Statistical methods for quantitative mass spectrometry proteomic experiments with labeling. BMC Bioinformatics 2012, 13(Suppl 16):S7.
• [52]Westman JO, Taherzadeh MJ, Franzen CJ: Proteomic analysis of the increased stress tolerance of saccharomyces cerevisiae encapsulated in liquid core alginate-chitosan capsules. PLoS One 2012, 7(11):e49335.
• [53]Gao J, Xu D, Sabat G, Valdivia H, Xu W, Shi NQ: Disrupting KATP channels diminishes the estrogen-mediated protection in female mutant mice during ischemia-reperfusion. Clinical Proteomics 2014, 11(1):19. BioMed Central Full Text
• [54]Zheng D, Xu L, Sun L, Feng Q, Wang Z, Shao G, Ni Y: Comparison of the ventricle muscle proteome between patients with rheumatic heart disease and controls with mitral valve prolapse: HSP 60 may be a specific protein in RHD. Biomed Res Int 2014, 2014:151726.