Investigation of protein network of proteins in cardiovascular disease

authors:

avatar Akram Safaei , avatar Mostafa Rezaei-Tavirani ORCID , * , avatar Mona Zamanian Azodi


how to cite: Safaei A, Rezaei-Tavirani M, Zamanian Azodi M. Investigation of protein network of proteins in cardiovascular disease. koomesh. 2017;19(4):e152925. 

Abstract

Introduction: Cardiovascular disease (CVD) that involved heart and vessels of heart, is one of the most common reasons of death in the world and unfortunately there are limitations in early diagnosis of this disease. In this study it has been survived the protein-protein interaction network in order to discover special biomarkers for early diagnosis of disease and timely treatment. Materials and Methods: In this study, involved proteins in cardiovascular disease have been collected using OMIM, Poly search and Wiki pathway databases and then these proteins have been matched on protein-protein interaction network. Topological analysis of network has been done with Cytoscape 3.3.Meaningly, degree and betweeness parameters have been considered to introduce the candidate markers. Results: After network topological analysis, proteins with higher degree have been recognized as hub and proteins with higher betweenness as bottleneck. It has been introduced 3 hub-bottleneck proteins as candidate biomarkers which have high centrality in network. Conclusion: MMP9, IL6 and AKT1 have been introduced as candidate proteins for CVD which can be diagnostic biomarkers or drug targets for this disease. In addition to, biochemical pathways for proteins in highest score sub-network were negative regulation of ion transport, collagen biosynthetic process, platelete degradation and extra cellular matrix disassembly

References

  • 1.

    Naghavi M, Wang H, Lozano R, Davis A, Liang X, Zhou M, et al. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 385: 117-171.

  • 2.

    Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, et al. Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA Task Force on Risk Reduction. Circulation 1998; 97: 1876-1887.

  • 3.

    Grundy SM, Bilheimer CD, Blackburn H, Brown WV, Kwiterovich Jr PO, et al. Rationale of the diet-heart statement of the American heart association report of nutrition committee. Circulation 1982; 17: 16-20.

  • 4.

    Kratz M. Dietary cholesterol, atherosclerosis and coronary heart disease. Atherosclerosis: Diet and Drugs: Springer; 2005; p. 195-213.

  • 5.

    Kasper D, Braunwald E, Fauci A, Hauser S, Longo D. Approach to the patient with cardiovascular disease: disorders of the cardiovascular system: Harrison's principles of internal medicine. New York: McGraw-Hill; 2008; p. 442-450.

  • 6.

    Amani F, Hajizadeh E, Hoseinian F. Survival rate in MI patients. Koomesh 2008; 9: 131-138.

  • 7.

    Lubell DL. Drawbacks and limitations of computed tomography. Tex Heart Inst J 2005; 32: 250-255.

  • 8.

    Price AN, Cheung KK, Cleary JO, Campbell AE, Riegler J, Lythgoe MF. Cardiovascular magnetic resonance imaging in experimental models. Open Cardiovasc Med J 2010; 4: 278-292.

  • 9.

    Karakas M, Koenig W. CRP in cardiovascular disease. Herz 2009; 34: 607-613.

  • 10.

    Ridker PM. C-reactive protein: eighty years from discovery to emergence as a major risk marker for cardiovascular disease. Clinic Chem 2009; 55: 209-215.

  • 11.

    Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the speedwell study are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001; 21: 603-610.

  • 12.

    McGregor E, Dunn MJ. Proteomics of heart disease. Hum Mol Genet 2003; 12: 135-144.

  • 13.

    Sharma P, Cosme J, Gramolini AO. Recent proteomic advances in cardiac cells. J Proteomics 2013; 81: 3-10.

  • 14.

    Askevold ET, Gullestad L, Nymo S, Kjekshus J, Yndestad A, Latini R, et al. Ecreted frizzled related protein 3 in chronic heart failure: analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA). PLoS One 2015; 10: e0133970.

  • 15.

    Hochholzer W, Morrow DA, Giugliano RP. Novel biomarkers in cardiovascular disease: update 2010. Am Heart J 2010; 160: 583-594.

  • 16.

    Deng N, Zhang J, Zong C, Wang Y, Lu H, Yang P, et al. Phosphoproteome analysis reveals regulatory sites in major pathways of cardiac mitochondria. Mol Cell Proteomics 2011; 10: 110-117.

  • 17.

    Safari-Alighiarloo N, Taghizadeh M, Rezaei-Tavirani M, Goliaei B, Peyvandi AA. Protein-protein interaction networks (PPI) and complex diseases. Gastroenterol Hepatol Bed Bench 2014; 7: 17-31.

  • 18.

    Safaei A, Tavirani MR, Oskouei AA, Azodi MZ, Mohebbi SR, Nikzamir AR. Protein-protein interaction network analysis of cirrhosis liver disease. Gastroenterol Hepatol Bed Bench 2016; 9: 114-123.

  • 19.

    Zamanian-Azodi M, Rezaei-Tavirani M, Rahmati-Rad S, Hasanzadeh H, Tavirani MR, Seyyedi SS. Protein-Protein Interaction Network could reveal the relationship between the breast and colon cancer. Gastroenterol Hepatol Bed Bench 2015; 8: 215-224.

  • 20.

    Rezaei-Tavirani M, Zamanian-Azodi M, Rajabi S, Masoudi-Nejad A, Rostami-Nejad M, Rahmatirad S. Protein clustering and interactome analysis in parkinson and Alzheimer's diseases. Arch Iran Med 2016; 19: 101-109.

  • 21.

    Abad S, Alijani S, Kia H, Zali H, Karim S, Pashaie M. Bioinformatics analysis of E. coli causing mastitis in Holstein dairy cattle by using microarray data. Koomesh 2015; 17: 214-223.

  • 22.

    Re M, Mesiti M, Valentini G. A fast ranking algorithm for predicting gene functions in biomolecular networks. IEEE/ACM Trans Comput Biol Bioinform 2012; 9: 1812-1818.

  • 23.

    Mostafavi S, Ray D, Warde-Farley D, Grouios C, Morris Q. GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome Biol 2008; 9: S4.

  • 24.

    Zali H, Tavirani MR. Meningioma protein-protein interaction network. Arch Iran Med 2014; 17: 262-272.

  • 25.

    Yu H, Kim PM, Sprecher E, Trifonov V, Gerstein M. The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics. PLoS Comput Biol 2007; 3: e59.

  • 26.

    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003; 13: 2498-2504.

  • 27.

    Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, et al. STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013; 41: 808-815.

  • 28.

    Rivera CG, Vakil R, Bader JS. NeMo: network module identification in Cytoscape. BMC Bioinformatics 2010; 11: S61.

  • 29.

    Liu H, Hu ZZ, Wu CH. DynGO: a tool for visualizing and mining of Gene Ontology and its associations. BMC Bioinformatics 2005; 6: 201-209.

  • 30.

    Jeong H, Mason SP, Barabsi A-L, Oltvai ZN. Lethality and centrality in protein networks. Nature 2001; 411: 41-42.

  • 31.

    Barabasi AL, Oltvai ZN. Network biology: understanding the cell's functional organization. Nat Rev Genet 2004; 5: 101-113.

  • 32.

    Consortium I-RMRA. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet 2012; 379: 1214-1224.

  • 33.

    Barallobre-Barreiro J, Didangelos A, Schoendube FA, Drozdov I, Yin X, Fernndez-Caggiano M, et al. Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia/reperfusion injury. Circulation 2012; 125: 789-802.

  • 34.

    Chaanine AH, Hajjar RJ. AKT signalling in the failing heart. Eur J Heart Fail 2011; 13: 825-829.

  • 35.

    Bader GD, Hogue CW. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics 2003; 4: 1-9.

  • 36.

    Chien KR. Molecular basis of cardiovascular disease: Saunders; 2004; p. 30-35.

  • 37.

    Guffanti A. Modeling molecular networks: a systems biology approach to gene function. Genome Biol 2002; 3: 4031.1-3.

  • 38.

    Bakail M, Ochsenbein F. Targeting proteinprotein interactions, a wide open field for drug design. Curr Pharm Biotechnol 2016; 19: 19-27.

  • 39.

    Weber KT. Extracellular matrix remodeling in heart failure a role for de novo angiotensin II generation. Circulation 1997; 96: 4065-4082.

  • 40.

    Rodriguez-Feo J, Sluijter J, de Kleijn D, Pasterkamp G. Modulation of collagen turnover in cardiovascular disease. Curr Pharm Des 2005; 11: 2501-2514.

  • 41.

    Luneva O, Brazhe N, Maksimova N, Rodnenkov O, Parshina EY, Bryzgalova NY, et al. Ion transport, membrane fluidity and haemoglobin conformation in erythrocyte from patients with cardiovascular diseases: role of augmented plasma cholesterol. Pathophysiol 2007; 14: 41-46.

  • 42.

    Ferguson-Smith AC, Chen Y-F, Newman MS, May LT, Sehgal PB, Ruddle FH. Regional localization of the interferon-2B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21. Genomics 1988; 2: 203-208.

  • 43.

    van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF. Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia. J Infect Dis 1997; 176: 439-444.

  • 44.

    Luc G, Bard JM, Juhan-Vague I, Ferrieres J, Evans A, Amouyel P, et al. C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease The PRIME study. Arterioscler Thromb Vasc Biol 2003; 23: 1255-1261.

  • 45.

    Shlipak MG, Ix JH, Bibbins-Domingo K, Lin F, Whooley MA. Biomarkers to predict recurrent cardiovascular disease: the Heart and Soul Study. Am J Med 2008; 121: 50-57.

  • 46.

    Lee JK, Bettencourt R, Brenner D, Le TA, Barrett-Connor E, Loomba R. Association between serum interleukin-6 concentrations and mortality in older adults: the Rancho Bernardo study. PLoS One 2012; 7: e34218.

  • 47.

    Van der Poll T, Levi M, Hack CE, Ten Cate H, Van Deventer S, Eerenberg A, et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 1994; 179: 1253-1259.

  • 48.

    Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993; 77: 1690-1694.

  • 49.

    Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, et al. Primary prevention of coronary heart disease: guidance from framingham a statement for healthcare professionals from the AHA task force on risk reduction. Circulation 1998; 97: 1876-1887.

  • 50.

    Blankenberg S, Rupprecht HJ, Poirier O, Bickel C, Smieja M, Hafner G, et al. Plasma concentrations and genetic variation of matrix metalloproteinase 9 and prognosis of patients with cardiovascular disease. Circulation 2003; 107: 1579-1585.

  • 51.

    Ferroni P, Basili S, Martini F, Cardarello CM, Ceci F, Di Franco M, et al. Serum metalloproteinase 9 levels in patients with coronary artery disease: a novel marker of inflammation. J Investig Med 2003; 51: 295-300.

  • 52.

    Hou Zh, Lu B, Gao Y, Cao Hl, Yu Ff, Jing N, et al. Matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) levels in patients with nonobstructive coronary artery disease detected by coronary computed tomographic angiography. Acad Radio 2013; 20: 25-31.

  • 53.

    Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and atherosclerotic plaque rupture. Physiol Rev 2005; 85: 1-31.

  • 54.

    Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 1996; 98: 2572-2579.

  • 55.

    Mohammed F, Smookler D, Khokha R. Metalloproteinases, inflammation, and rheumatoid arthritis. Ann Rheum Dis 2003; 62: 43-47.

  • 56.

    Abeyrathna P, Su Y. The critical role of Akt in cardiovascular function. Vascul Pharmacol 2015; 74: 38-48.

  • 57.

    Shiraishi I, Melendez J, Ahn Y, Skavdahl M, Murphy E, Welch S, et al. Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes. Circ Res 2004; 94: 884-891.

  • 58.

    Lpez B, Gonzlez A, Dez J. Circulating biomarkers of collagen metabolism in cardiac diseases. Circulation 2010; 12: 1645-1654.