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Erschienen in: Herz 1/2017

30.06.2016 | Original articles

Identifying disrupted pathways by tracking altered modules in type 2 DM-related heart failure

verfasst von: H. Liu, X. Han, Y. Li

Erschienen in: Herz | Ausgabe 1/2017

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Abstract

Background

This study aimed to screen disrupted pathways in type 2 diabetes mellitus (T2DM) heart failure by systematically tracking the altered modules of reweighted protein–protein interaction (PPI) networks.

Methods

We implemented systematic identification and comparison of modules across non-T2DM and T2DM heart failure subjects by integrating gene expression data and PPI networks. The PPI networks of non-T2DM heart failure and T2DM heart failure were constructed and reweighted by means of Spearman’s correlation coefficient (SCC). Subsequently, a clique-merging algorithm was used to explore the modules in the PPI network, followed by the identification of disrupted modules based on a maximum-weight bipartite matching and sorting in descending order. Finally, pathway enrichment analyses were conducted for genes in disrupted modules to determine the biological pathways in T2DM heart failure.

Results

By comparing the modules of non-T2DM heart failure and T2DM heart failure, 804 disrupted modules were explored. The genes in disrupted modules were significantly enriched in 39 categories (p < 1.00E-06). Of these, the most significant pathways were the focal adhesion, vascular endothelial growth factor (VEGF) signaling, and mitogen-activated protein kinase (MAPK) signaling pathways.

Conclusion

The identified disrupted pathways – focal adhesion, VEGF signaling, and MAPK signaling – might play important roles in the progression of T2DM heart failure.
Literatur
2.
3.
Zurück zum Zitat Struthers AD, Morris AD (2002) Screening for and treating left-ventricular abnormalities in diabetes mellitus: A new way of reducing cardiac deaths. Lancet 359(9315):1430–1432CrossRefPubMed Struthers AD, Morris AD (2002) Screening for and treating left-ventricular abnormalities in diabetes mellitus: A new way of reducing cardiac deaths. Lancet 359(9315):1430–1432CrossRefPubMed
4.
Zurück zum Zitat Stone PH et al (1989) The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: Contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 14(1):49–57CrossRefPubMed Stone PH et al (1989) The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: Contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 14(1):49–57CrossRefPubMed
5.
Zurück zum Zitat Estep JD, Aguilar D (2006) Diabetes and heart failure in the post-myocardial infarction patient. Curr Heart Fail Rep 3(4):164–169CrossRefPubMed Estep JD, Aguilar D (2006) Diabetes and heart failure in the post-myocardial infarction patient. Curr Heart Fail Rep 3(4):164–169CrossRefPubMed
6.
Zurück zum Zitat Hotamisligil GS, Shargill NS (1993) Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMed Hotamisligil GS, Shargill NS (1993) Adipose expression of tumor necrosis factor-alpha: Direct role in obesity-linked insulin resistance. Science 259(5091):87–91CrossRefPubMed
7.
Zurück zum Zitat Volz HC et al (2010) HMGB1: The missing link between diabetes mellitus and heart failure. Basic Res Cardiol 105(6):805–820CrossRefPubMed Volz HC et al (2010) HMGB1: The missing link between diabetes mellitus and heart failure. Basic Res Cardiol 105(6):805–820CrossRefPubMed
8.
Zurück zum Zitat Heather LC, Clarke K (2011) Metabolism, hypoxia and the diabetic heart. J Mol Cell Cardiol 50(4):598–605CrossRefPubMed Heather LC, Clarke K (2011) Metabolism, hypoxia and the diabetic heart. J Mol Cell Cardiol 50(4):598–605CrossRefPubMed
10.
Zurück zum Zitat Gavin AC et al (2006) Proteome survey reveals modularity of the yeast cell machinery. Nature 440(7084):631–636CrossRefPubMed Gavin AC et al (2006) Proteome survey reveals modularity of the yeast cell machinery. Nature 440(7084):631–636CrossRefPubMed
11.
Zurück zum Zitat Zhao J et al (2012) Efficient methods for identifying mutated driver pathways in cancer. Bioinformatics 28(22):2940–2947CrossRefPubMed Zhao J et al (2012) Efficient methods for identifying mutated driver pathways in cancer. Bioinformatics 28(22):2940–2947CrossRefPubMed
12.
Zurück zum Zitat Jordán F, Nguyen TP, Liu WC (2012) Studying protein-protein interaction networks: a systems view on diseases. Brief Funct Genomics 11(6):497–504CrossRefPubMed Jordán F, Nguyen TP, Liu WC (2012) Studying protein-protein interaction networks: a systems view on diseases. Brief Funct Genomics 11(6):497–504CrossRefPubMed
13.
Zurück zum Zitat Chao W et al (2012) Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC Bioinformatics 13(14):182 Chao W et al (2012) Integrating gene expression and protein-protein interaction network to prioritize cancer-associated genes. BMC Bioinformatics 13(14):182
14.
Zurück zum Zitat Liu G, Wong L, Chua HN (2009) Complex discovery from weighted PPI networks. Bioinformatics 25(15):1891–1897CrossRefPubMed Liu G, Wong L, Chua HN (2009) Complex discovery from weighted PPI networks. Bioinformatics 25(15):1891–1897CrossRefPubMed
15.
Zurück zum Zitat Srihari S, Ragan MA (2013) Systematic tracking of dysregulated modules identifies novel genes in cancer. Bioinformatics 29(12):1553–1561CrossRefPubMed Srihari S, Ragan MA (2013) Systematic tracking of dysregulated modules identifies novel genes in cancer. Bioinformatics 29(12):1553–1561CrossRefPubMed
17.
Zurück zum Zitat Irizarry RA et al (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31:4CrossRef Irizarry RA et al (2003) Summaries of Affymetrix GeneChip probe level data. Nucleic Acids Res 31:4CrossRef
18.
Zurück zum Zitat Bolstad BM et al (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19(2):185–193CrossRefPubMed Bolstad BM et al (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19(2):185–193CrossRefPubMed
19.
Zurück zum Zitat Szklarczyk D et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39(suppl 1):D561–D568CrossRefPubMed Szklarczyk D et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39(suppl 1):D561–D568CrossRefPubMed
20.
Zurück zum Zitat Hauke J, Kossowski T (2011) Comparison of values of Pearson’s and Spearman’s correlation coefficients on the same sets of data. Quaestiones Geogr 30(2):87–93 Hauke J, Kossowski T (2011) Comparison of values of Pearson’s and Spearman’s correlation coefficients on the same sets of data. Quaestiones Geogr 30(2):87–93
21.
Zurück zum Zitat Srihari S, Leong HW (2013) A survey of computational methods for protein complex prediction from protein interaction networks. J Bioinform Comput Biol 11(02):1230002CrossRefPubMed Srihari S, Leong HW (2013) A survey of computational methods for protein complex prediction from protein interaction networks. J Bioinform Comput Biol 11(02):1230002CrossRefPubMed
22.
Zurück zum Zitat Tomita E, Tanaka A, Takahashi H (2006) The worst-case time complexity for generating all maximal cliques and computational experiments. Theor Comput Sci 363(1):28–42CrossRef Tomita E, Tanaka A, Takahashi H (2006) The worst-case time complexity for generating all maximal cliques and computational experiments. Theor Comput Sci 363(1):28–42CrossRef
23.
Zurück zum Zitat Gabow HN (1976) An efficient implementation of Edmonds’ algorithm for maximum matching on graphs. J Acm 23(2):221–234 (JACM)CrossRef Gabow HN (1976) An efficient implementation of Edmonds’ algorithm for maximum matching on graphs. J Acm 23(2):221–234 (JACM)CrossRef
24.
Zurück zum Zitat Huang DW, Sherman BT, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57CrossRef Huang DW, Sherman BT, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57CrossRef
25.
Zurück zum Zitat Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc 72(4):289–300 (Series B (Methodological)) Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc 72(4):289–300 (Series B (Methodological))
26.
Zurück zum Zitat Shah AD et al (2015) Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol 3(14):105–113CrossRefPubMedPubMedCentral Shah AD et al (2015) Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol 3(14):105–113CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Chen CS et al (2003) Cell shape provides global control of focal adhesion assembly. Biochem Biophys Res Commun 307(2):355–361CrossRefPubMed Chen CS et al (2003) Cell shape provides global control of focal adhesion assembly. Biochem Biophys Res Commun 307(2):355–361CrossRefPubMed
28.
Zurück zum Zitat Taylor JM, Rovin JD, Parsons JT (2000) A role for focal adhesion kinase in phenylephrine-induced hypertrophy of rat ventricular cardiomyocytes. J Biol Chem 275(25):19250–19257CrossRefPubMed Taylor JM, Rovin JD, Parsons JT (2000) A role for focal adhesion kinase in phenylephrine-induced hypertrophy of rat ventricular cardiomyocytes. J Biol Chem 275(25):19250–19257CrossRefPubMed
30.
Zurück zum Zitat Bayer AL et al (2002) PYK2 expression and phosphorylation increases in pressure overload-induced left ventricular hypertrophy. Am J Physiol Heart Circ Physiol 283(2):H695–H706CrossRefPubMed Bayer AL et al (2002) PYK2 expression and phosphorylation increases in pressure overload-induced left ventricular hypertrophy. Am J Physiol Heart Circ Physiol 283(2):H695–H706CrossRefPubMed
31.
Zurück zum Zitat Lopes MM et al (2007) Increased expression and phosphorylation of focal adhesion kinase correlates with dysfunction in the volume-overloaded human heart. Clin Sci 113(3–4):195–204CrossRefPubMed Lopes MM et al (2007) Increased expression and phosphorylation of focal adhesion kinase correlates with dysfunction in the volume-overloaded human heart. Clin Sci 113(3–4):195–204CrossRefPubMed
32.
Zurück zum Zitat Eble DM et al (2000) Endothelin-induced cardiac myocyte hypertrophy: Role for focal adhesion kinase. Ajp Heart Circ Physiol 278(5):H1695–H707 Eble DM et al (2000) Endothelin-induced cardiac myocyte hypertrophy: Role for focal adhesion kinase. Ajp Heart Circ Physiol 278(5):H1695–H707
33.
Zurück zum Zitat Shen E et al (2011) MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte hypertrophy. Am J Pathol 179(2):639–650CrossRefPubMedPubMedCentral Shen E et al (2011) MicroRNAs involved in the mitogen-activated protein kinase cascades pathway during glucose-induced cardiomyocyte hypertrophy. Am J Pathol 179(2):639–650CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611CrossRefPubMed Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25(4):581–611CrossRefPubMed
35.
Zurück zum Zitat Landray MJ et al (2004) Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study. Am J Kidney Dis p:244–253CrossRef Landray MJ et al (2004) Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study. Am J Kidney Dis p:244–253CrossRef
36.
Zurück zum Zitat Lip GY, Chung I (2005) Vascular endothelial growth factor and angiogenesis in heart failure. J Card Fail 11(4):285–287CrossRefPubMed Lip GY, Chung I (2005) Vascular endothelial growth factor and angiogenesis in heart failure. J Card Fail 11(4):285–287CrossRefPubMed
37.
Zurück zum Zitat Mutunga M et al (2001) Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med 163:195–200CrossRefPubMed Mutunga M et al (2001) Circulating endothelial cells in patients with septic shock. Am J Respir Crit Care Med 163:195–200CrossRefPubMed
38.
Zurück zum Zitat Shimojo N et al (2007) Contributory role of VEGF overexpression in endothelin-1-induced cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 293(1):H474–H481CrossRefPubMed Shimojo N et al (2007) Contributory role of VEGF overexpression in endothelin-1-induced cardiomyocyte hypertrophy. Am J Physiol Heart Circ Physiol 293(1):H474–H481CrossRefPubMed
39.
Zurück zum Zitat Sun J et al (2010) Intermittent high glucose enhances cell proliferation and VEGF expression in retinal endothelial cells: The role of mitochondrial reactive oxygen species. Mol Cell Biochem 343(1–2):27–35CrossRefPubMed Sun J et al (2010) Intermittent high glucose enhances cell proliferation and VEGF expression in retinal endothelial cells: The role of mitochondrial reactive oxygen species. Mol Cell Biochem 343(1–2):27–35CrossRefPubMed
40.
41.
Zurück zum Zitat Cheng YC et al (2009) Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2 cardiomyoblast cells. Mol Cell Biochem 325(1–2):15–23CrossRefPubMed Cheng YC et al (2009) Lipopolysaccharide upregulates uPA, MMP-2 and MMP-9 via ERK1/2 signaling in H9c2 cardiomyoblast cells. Mol Cell Biochem 325(1–2):15–23CrossRefPubMed
42.
Zurück zum Zitat Chang SH et al (2011) Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ–induced DM Rats. Evidence-based Complementary Altern Med 2011(1):1–11 Chang SH et al (2011) Garlic Oil Alleviates MAPKs- and IL-6-mediated Diabetes-related Cardiac Hypertrophy in STZ–induced DM Rats. Evidence-based Complementary Altern Med 2011(1):1–11
43.
Zurück zum Zitat Kuo WW et al (2011) Attenuated cardiac Mitochondrial-dependent Apoptotic effects by Li-Fu formula in hamsters fed with a Hypercholesterol diet. Evid Based Complement Alternat Med 2011(5):530345PubMedPubMedCentral Kuo WW et al (2011) Attenuated cardiac Mitochondrial-dependent Apoptotic effects by Li-Fu formula in hamsters fed with a Hypercholesterol diet. Evid Based Complement Alternat Med 2011(5):530345PubMedPubMedCentral
Metadaten
Titel
Identifying disrupted pathways by tracking altered modules in type 2 DM-related heart failure
verfasst von
H. Liu
X. Han
Y. Li
Publikationsdatum
30.06.2016
Verlag
Springer Medizin
Erschienen in
Herz / Ausgabe 1/2017
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI
https://doi.org/10.1007/s00059-016-4445-1

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