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McGarrity S, Halldórsson H, Palsson S, et al. Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling. Front Cardiovasc Med. 2016;3:10doi: 10.3389/fcvm.2016.00010.
McGarrity, S., Halldórsson, H., Palsson, S., Johansson, P. I., & Rolfsson, �. �. (2016). Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling. Frontiers in cardiovascular medicine, 310. https://doi.org/10.3389/fcvm.2016.00010
McGarrity, Sarah, et al. "Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling." Frontiers in cardiovascular medicine vol. 3 (2016): 10. doi: https://doi.org/10.3389/fcvm.2016.00010
McGarrity S, Halldórsson H, Palsson S, Johansson PI, Rolfsson Ó. Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling. Front Cardiovasc Med. 2016 Apr 18;3:10. doi: 10.3389/fcvm.2016.00010. eCollection 2016. PMID: 27148541; PMCID: PMC4834436.
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Front Cardiovasc Med. 2016 Apr 18;3:10. doi: 10.3389/fcvm.2016.00010. eCollection 2016.

Understanding the Causes and Implications of Endothelial Metabolic Variation in Cardiovascular Disease through Genome-Scale Metabolic Modeling.

Frontiers in cardiovascular medicine

Sarah McGarrity, Haraldur Halldórsson, Sirus Palsson, Pär I Johansson, Óttar Rolfsson

Affiliations

  1. Center for Systems Biology, University of Iceland , Reykjavik , Iceland.
  2. Department of Pharmacology and Toxicology, School of Health Sciences, University of Iceland , Reykjavik , Iceland.
  3. Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Sinopia Biosciences Inc., San Diego, CA, USA.
  4. Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
  5. Center for Systems Biology, University of Iceland, Reykjavik, Iceland; Department of Biochemistry and Molecular Biology, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

PMID: 27148541 PMCID: PMC4834436 DOI: 10.3389/fcvm.2016.00010

Abstract

High-throughput biochemical profiling has led to a requirement for advanced data interpretation techniques capable of integrating the analysis of gene, protein, and metabolic profiles to shed light on genotype-phenotype relationships. Herein, we consider the current state of knowledge of endothelial cell (EC) metabolism and its connections to cardiovascular disease (CVD) and explore the use of genome-scale metabolic models (GEMs) for integrating metabolic and genomic data. GEMs combine gene expression and metabolic data acting as frameworks for their analysis and, ultimately, afford mechanistic understanding of how genetic variation impacts metabolism. We demonstrate how GEMs can be used to investigate CVD-related genetic variation, drug resistance mechanisms, and novel metabolic pathways in ECs. The application of GEMs in personalized medicine is also highlighted. Particularly, we focus on the potential of GEMs to identify metabolic biomarkers of endothelial dysfunction and to discover methods of stratifying treatments for CVDs based on individual genetic markers. Recent advances in systems biology methodology, and how these methodologies can be applied to understand EC metabolism in both health and disease, are thus highlighted.

Keywords: endothelium; genetics; metabolic modeling; metabolism; metabolomics; personalized/precision medicine

References

  1. Am J Physiol. 1999 Mar;276(3 Pt 1):G743-50 - PubMed
  2. Biochem Biophys Res Commun. 1999 Nov;265(1):112-5 - PubMed
  3. Comp Biochem Physiol A Mol Integr Physiol. 2000 May;126(1):115-23 - PubMed
  4. J Biol Chem. 2000 Dec 22;275(51):40042-7 - PubMed
  5. Diabetes Care. 2000 Dec;23(12):1830-4 - PubMed
  6. Blood. 2000 Dec 1;96(12):4005-6 - PubMed
  7. Diabetologia. 2001 Feb;44(2):196-202 - PubMed
  8. J Mol Cell Cardiol. 2001 Apr;33(4):671-9 - PubMed
  9. Circ Res. 2001 Jun 22;88(12):1276-82 - PubMed
  10. J Clin Invest. 2001 Nov;108(9):1341-8 - PubMed
  11. Biochem J. 2002 Mar 15;362(Pt 3):733-9 - PubMed
  12. Circulation. 2002 Jul 23;106(4):466-72 - PubMed
  13. J Clin Invest. 2003 Apr;111(8):1201-9 - PubMed
  14. J Clin Invest. 2003 Oct;112(7):1049-57 - PubMed
  15. Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):998-1005 - PubMed
  16. Clin Hemorheol Microcirc. 2004;30(3-4):181-4 - PubMed
  17. Circ Res. 2004 Aug 6;95(3):233-8 - PubMed
  18. J Biol Chem. 2005 Apr 1;280(13):12888-95 - PubMed
  19. Curr Opin Cardiol. 2005 Nov;20(6):547-51 - PubMed
  20. J Clin Invest. 2006 Jan;116(1):49-58 - PubMed
  21. J Theor Biol. 2006 Aug 7;241(3):564-89 - PubMed
  22. Ann Biomed Eng. 2006 Apr;34(4):605-17 - PubMed
  23. Am J Physiol Renal Physiol. 2006 Aug;291(2):F297-304 - PubMed
  24. Arterioscler Thromb Vasc Biol. 2006 Oct;26(10):2275-80 - PubMed
  25. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82 - PubMed
  26. Am J Epidemiol. 2007 May 1;165(9):1076-87 - PubMed
  27. Nat Protoc. 2007;2(3):727-38 - PubMed
  28. Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1796-802 - PubMed
  29. Med Eng Phys. 2008 Jun;30(5):647-60 - PubMed
  30. J Physiol Sci. 2007 Oct;57(5):299-309 - PubMed
  31. Biogerontology. 2008 Aug;9(4):247-59 - PubMed
  32. J Inherit Metab Dis. 2008 Jun;31(3):412-7 - PubMed
  33. Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H815-22 - PubMed
  34. Mol Syst Biol. 2009;5:263 - PubMed
  35. Cell. 2009 Jun 12;137(6):1124-35 - PubMed
  36. Nat Protoc. 2010 Jan;5(1):93-121 - PubMed
  37. Nitric Oxide. 2010 Aug 1;23(1):1-11 - PubMed
  38. Trends Biochem Sci. 2010 Oct;35(10):547-55 - PubMed
  39. Cardiovasc Res. 2010 Dec 1;88(3):512-9 - PubMed
  40. Oxid Med Cell Longev. 2009 Jul-Aug;2(3):172-5 - PubMed
  41. Atherosclerosis. 2010 Nov;213(1):329-31 - PubMed
  42. J Mol Cell Cardiol. 1990 Dec;22(12):1393-404 - PubMed
  43. Circulation. 2010 Nov 2;122(18 Suppl 3):S640-56 - PubMed
  44. BMB Rep. 2011 Jun;44(6):415-20 - PubMed
  45. Free Radic Biol Med. 2011 Oct 1;51(7):1411-27 - PubMed
  46. BMC Syst Biol. 2011 Jul 15;5:112 - PubMed
  47. BMC Syst Biol. 2011 Oct 01;5:155 - PubMed
  48. J Clin Bioinforma. 2011 Oct 26;1(1):29 - PubMed
  49. Atherosclerosis. 2012 Feb;220(2):443-8 - PubMed
  50. J Biol Chem. 1990 Nov 15;265(32):19461-6 - PubMed
  51. PLoS Comput Biol. 2012;8(5):e1002518 - PubMed
  52. Scand J Rheumatol. 2012 Oct;41(5):350-3 - PubMed
  53. World J Biol Chem. 2012 Jun 26;3(6):121-6 - PubMed
  54. Pflugers Arch. 2012 Dec;464(6):657-69 - PubMed
  55. Cardiovasc Diabetol. 2013 Jan 02;12:1 - PubMed
  56. Pac Symp Biocomput. 2013;:385-96 - PubMed
  57. Am J Physiol Heart Circ Physiol. 2013 Jun 1;304(11):H1455-70 - PubMed
  58. PLoS Comput Biol. 2013;9(3):e1002980 - PubMed
  59. Biotechnol J. 2013 Sep;8(9):985-96 - PubMed
  60. Front Physiol. 2013 Apr 25;4:92 - PubMed
  61. Free Radic Biol Med. 2013 Oct;63:161-74 - PubMed
  62. J Appl Physiol (1985). 2013 Aug 1;115(3):383-93 - PubMed
  63. Biophys J. 2013 May 21;104(10):2295-306 - PubMed
  64. Comput Methods Biomech Biomed Engin. 2015;18(4):351-61 - PubMed
  65. Cell. 2013 Aug 1;154(3):651-63 - PubMed
  66. Circulation. 2013 Sep 10;128(11 Suppl 1):S50-S58 - PubMed
  67. Front Physiol. 2013 Sep 24;4:260 - PubMed
  68. PLoS One. 2013 Sep 26;8(9):e75984 - PubMed
  69. Nat Commun. 2013;4:2632 - PubMed
  70. Nat Rev Genet. 2014 Feb;15(2):107-20 - PubMed
  71. Mol Syst Biol. 2014 Mar 19;10:721 - PubMed
  72. Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1231-9 - PubMed
  73. Nitric Oxide. 2014 May 30;39:1-7 - PubMed
  74. PLoS Comput Biol. 2014 Apr 24;10(4):e1003580 - PubMed
  75. Neuropathol Appl Neurobiol. 2015 Aug;41(5):646-56 - PubMed
  76. Circ Cardiovasc Genet. 2014 Aug;7(4):407-15 - PubMed
  77. Eur Rev Med Pharmacol Sci. 2014;18(14):2025-30 - PubMed
  78. PLoS One. 2014 Jul 16;9(7):e102319 - PubMed
  79. J Cardiol. 2015 Apr;65(4):311-7 - PubMed
  80. PLoS One. 2014 Jul 29;9(7):e103260 - PubMed
  81. PLoS One. 2014 Aug 15;9(8):e105383 - PubMed
  82. J Proteome Res. 2014 Nov 7;13(11):5106-19 - PubMed
  83. J Clin Diagn Res. 2014 Aug;8(8):CC04-6 - PubMed
  84. Diabetes Care. 2015 Jan;38(1):119-25 - PubMed
  85. Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):137-45 - PubMed
  86. Biomech Model Mechanobiol. 2015 Jun;14(3):665-78 - PubMed
  87. Eur Rev Med Pharmacol Sci. 2014;18(23):3593-600 - PubMed
  88. Amino Acids. 2015 Mar;47(3):435-47 - PubMed
  89. J Exerc Nutrition Biochem. 2014 Sep;18(3):239-47 - PubMed
  90. Mol Cell Proteomics. 2015 Mar;14(3):621-34 - PubMed
  91. Biomed Eng Online. 2015;14 Suppl 1:S7 - PubMed
  92. Bioessays. 2015 Jun;37(6):588-91 - PubMed
  93. Nucleosides Nucleotides Nucleic Acids. 2015;34(4):246-57 - PubMed
  94. Circ Res. 2015 Mar 27;116(7):1231-44 - PubMed
  95. Nature. 2015 Apr 9;520(7546):192-197 - PubMed
  96. Nucleic Acids Res. 2015 Apr 30;43(8):3899-910 - PubMed
  97. J Dev Drugs. 2013 Oct;2(2):null - PubMed
  98. J Cell Biol. 2015 Apr 13;209(1):13-22 - PubMed
  99. Cell Rep. 2015 May 12;11(6):921-933 - PubMed
  100. Iran J Basic Med Sci. 2015 Mar;18(3):267-76 - PubMed
  101. Eur J Prev Cardiol. 2016 Mar;23(5):502-10 - PubMed
  102. Gene. 2015 Sep 1;568(2):165-9 - PubMed
  103. Adv Exp Med Biol. 2015;858:1-7 - PubMed
  104. Cell Prolif. 2015 Aug;48(4):475-85 - PubMed
  105. PLoS One. 2015 Jul 08;10(7):e0131537 - PubMed
  106. PLoS One. 2015 Jul 09;10(7):e0131439 - PubMed
  107. Physiol Rep. 2015 Jul;3(7):null - PubMed
  108. Front Physiol. 2015 Jul 07;6:194 - PubMed
  109. Gene. 2015 Dec 10;574(1):76-81 - PubMed
  110. Int Arch Occup Environ Health. 2016 Apr;89(3):435-48 - PubMed
  111. Semin Thromb Hemost. 2015 Sep;41(6):549-55 - PubMed
  112. Clin Physiol Funct Imaging. 2017 May;37(3):243-254 - PubMed
  113. Eur Heart J. 2015 Oct 21;36(40):2696-705 - PubMed
  114. Pharmacol Rep. 2015 Aug;67(4):682-8 - PubMed
  115. Am J Clin Nutr. 2015 Oct;102(4):745-56 - PubMed
  116. Diabetol Metab Syndr. 2015 Sep 17;7:81 - PubMed
  117. J Theor Biol. 2015 Dec 21;387:228-40 - PubMed
  118. Nitric Oxide. 2016 Jan 30;52:1-15 - PubMed
  119. Mediators Inflamm. 2015;2015:831059 - PubMed
  120. Brief Bioinform. 2016 Nov;17(6):1060-1069 - PubMed
  121. Cell Rep. 2015 Dec 1;13(9):2014-26 - PubMed
  122. Eur J Prev Cardiol. 2016 Jun;23(9):956-66 - PubMed
  123. Int J Epidemiol. 2015 Dec;44(6):1800-13 - PubMed
  124. Acta Physiol (Oxf). 2017 Jan;219(1):22-96 - PubMed
  125. J Intern Med. 2016 May;279(5):477-84 - PubMed
  126. PLoS Comput Biol. 2016 Mar 04;12(3):e1004808 - PubMed
  127. Cell Syst. 2015 Oct 28;1(4):283-92 - PubMed
  128. FEBS Lett. 1987 Dec 10;225(1-2):93-6 - PubMed
  129. Diabetes. 1970 Sep;19(9):644-55 - PubMed
  130. Biochim Biophys Acta. 1983 Apr 5;762(2):295-301 - PubMed
  131. Shock. 1995 Aug;4(2):79-88 - PubMed
  132. Mol Med. 1995 May;1(4):447-56 - PubMed
  133. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9220-5 - PubMed
  134. J Biol Chem. 1998 Oct 2;273(40):25804-8 - PubMed

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