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Data Mining as a Powerful Tool for Creating Novel Drugs in Cardiovascular Medicine: The Importance of a “Back-and-Forth Loop” Between Clinical Data and Basic Research

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Abstract

Cardiovascular diseases, which lead to cardiovascular events including death, progress with many deleterious pathophysiological sequels. If a cause-and-effect relationship follows a one‐to‐one relation, we can focus on a cause to treat an effect, but such a relation cannot be applied in cardiovascular diseases. To identify novel drugs in the cardiovascular field, we generally adopt two different strategies: induction and deduction. In the cardiovascular field, it is difficult to use deduction because cardiovascular diseases are caused by many factors, leading us to use induction. In this method, we consider all clinical data, such as medical records or genetic data, and identify a few candidates. Recent computational and mathematical advances enable us to use data-mining methods to uncover hidden relationships between many parameters and clinical outcomes. However, because these candidates are not identified as promoting or inhibiting factors, or as causal or consequent factors of cardiovascular diseases, we need to test them in basic research, and bring them back to the clinical field to test their efficacy in clinical trials. With such a “back-and-forth loop” between clinical observation and basic research, data-mining methods may provide novel strategies leading to new tools for clinicians, basic findings for researchers, and better outcomes for patients.

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References

  1. Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress. Circulation. 2000;102(20 Suppl 4):IV14–23.

    CAS  PubMed  Google Scholar 

  2. Ambrosy AP, Fonarow GC, Butler J, Chioncel O, Greene SJ, Vaduganathan M, et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J Am Coll Cardiol. 2014;63(12):1123–33.

    Article  PubMed  Google Scholar 

  3. Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation. 1988;77:721–30.

    Article  CAS  PubMed  Google Scholar 

  4. DeMaria AN. Translational research? J Am Coll Cardiol. 2013;62(24):2342–3.

    Article  PubMed  Google Scholar 

  5. Podgorelec V, Kokol P, Stiglic B, Rozman I. Decision trees: an overview and their use in medicine. Med Syst. 2002;26(5):445–63.

    Article  Google Scholar 

  6. Han J, Kamber M, Pei J. Data mining: concepts and techniques, Third Edition, The Morgan Kaufmann Series in Data Management Systems. Morgan Kaufmann, 2011.

  7. Mardia KV, Kent JT, Bibby JM. Multivariate analysis, Probability and mathematical statistics. Academic Press, 1979.

  8. Schoelkopf B, Smola AJ. Learning with Kernels: support vector machines, regularization, optimization, and beyond, adaptive computation and machine learning series. MIT Press, 2002.

  9. Pearl J. Causality: models, reasoning, and inference, Second Edition. Cambridge University Press, 2009.

  10. Aggarwal CC, Reddy CK. Data clustering: algorithms and applications, Chapman & Hall/CRC data mining and knowledge discovery series. Chapman & Hall/CRC Press, 2013.

  11. Aggarwal CC, Han J. Frequent pattern mining. Springer, 2014.

  12. Hodge V. Outlier and anomaly detection: a survey of outlier and anomaly detection methods. Lap Lambert Academic Publishing, 2011.

  13. Bernstein BE, Meissner A, Lande ES. The mammalian epigenome. Cell. 2007;128(4):669–81.

    Article  CAS  PubMed  Google Scholar 

  14. Davis RL, Weintraub H, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51(6):987–1000.

    Article  CAS  PubMed  Google Scholar 

  15. Lashkari DA, DeRisi JL, McCusker JH, Namath AF, Gentile C, Hwang SY, et al. Yeast microarrays for genome wide parallel genetic and gene expression analysis. Proc Natl Acad Sci U S A. 1997;94(24):13057–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, et al. A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. J Clin Invest. 2007;117(10):2812–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, et al. Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation. Proc Natl Acad Sci U S A. 2014;111(1):273–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Fareed M, Afza MI. Single nucleotide polymorphism in genome-wide association of human population: a tool for broad spectrum service. Egyptian J Med Hum Genet. 2013;14:123–34.

    Article  Google Scholar 

  19. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461(7261):252–6.

    Article  Google Scholar 

  20. Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6.

    Article  CAS  PubMed  Google Scholar 

  21. Steinberg D, Witztum JL. Inhibition of PCSK9: a powerful weapon for achieving ideal LDL cholesterol levels. Proc Natl Acad Sci U S A. 2009;106(24):9546–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet. 2014;383(9911):60–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Boch J. TALEs of genome targeting. Nature Biotechnol 29(2): 135–6.

  24. Marraffini LA, Sontheimer EJ. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nat Rev Genet. 2010;11(3):181–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Kim J, Washio T, Yamagishi M, Yasumura Y, Nakatani S, Hashimura K, et al. A novel data mining approach to the identification of effective drugs or combinations for targeted endpoints-application to chronic heart failure as a New form of evidence-based medicine. Cardiovasc Drugs Ther. 2004;18:483–9.

    Article  CAS  PubMed  Google Scholar 

  26. Hough LB. Genomics meets histamine receptors: new subtypes, new receptors. Mol Pharmacol. 2001;59:415–9.

    CAS  PubMed  Google Scholar 

  27. Leurs R, Bakker RA, Timmerman H, de Esch IJ. The histamine H3 receptor: from gene cloning to H3 receptor drugs. Nat Rev Drug Discov. 2005;4:107–20.

    Article  CAS  PubMed  Google Scholar 

  28. Gantz I, Schaffer M, DelValle J, Logsdon C, Campbell V, Uhler M, et al. Molecular cloning of a gene encoding the histamine H2 receptor. Proc Natl Acad Sci U S A. 1991;88:429–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Matsuda N, Jesmin S, Takahashi Y, Hatta E, Kobayashi M, Matsuyama K, et al. Histamine H1 and H2 receptor gene and protein levels are differentially expressed in the hearts of rodents and humans. J Pharmacol Exp Ther. 2004;309:786–95.

    Article  CAS  PubMed  Google Scholar 

  30. Hill SJ, Ganellin CR, Timmerman H, Schwartz JC, Shankley NP, Young JM, et al. International union of pharmacology. XIII. Classification of histamine receptors. Pharmacol Rev. 1997;49:253–78.

    CAS  PubMed  Google Scholar 

  31. Eckel L, Gristwood RW, Nawrath H, Owen DA, Satter P. Inotropic and electrophysiological effects of histamine on human ventricular heart muscle. J Physiol. 1982;330:111–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Du XY, Schoemaker RG, X462P6, Bos E, Saxena PR. Effects of histamine on porcine isolated myocardium: differentiation from effects on human tissue. J Cardiovasc Pharmacol 1993;22:468–73.

  33. Hattori Y. Cardiac histamine receptors: their pharmacological consequences and signal transduction pathways. Methods Find Exp Clin Pharmacol. 1999;21:123–31.

    Article  CAS  PubMed  Google Scholar 

  34. Kirch W, Halabi A, Hinrichsen H. Hemodynamic effects of quinidine and famotidine in patients with congestive heart failure. Clin Pharmacol Ther. 1992;51:325–33.

    Article  CAS  PubMed  Google Scholar 

  35. Maronle G. The role of mast cells in cardiovascular disease. In: Matsumori A, editor. Cardiomyopathies in heart failure: biomolecular, infectious and immune mechanisms. MA: Kluwer Academic Publishers; 2003. p. 185–228.

    Chapter  Google Scholar 

  36. Asanuma H, Minamino T, Ogai A, Kim J, Asakura M, Komamura K, et al. Blockade of histamine H2 receptors protects the heart against ischemia and reperfusion injury in dogs. J Mol Cell Cardiol. 2006;40(5):666–74.

    Article  CAS  PubMed  Google Scholar 

  37. Zeng Z, Shen L, Li X, Luo T, Wei X, Zhang J, et al. Disruption of histamine H2 receptor slows heart failure progression through reducing myocardial apoptosis and fibrosis. Clin Sci (Lond). 2014;127(7):435–48.

    Article  CAS  Google Scholar 

  38. Takahama H, Asanuma H, Sanada S, Fujita M, Sasaki H, Wakeno M, et al. A histamine H2 receptor blocker ameliorates development of heart failure in dogs independently of β-adrenergic receptor blockade. Basic Res Cardiol. 2010;105(6):787–94.

    Article  CAS  PubMed  Google Scholar 

  39. Kim J, Ogai A, Nakatani S, Hashimura K, Kanzaki H, Komamura K, et al. Impact of blockade of histamine H2 receptors on chronic heart failure revealed by retrospective and prospective randomized studies. J Am Coll Cardiol. 2006;48(7):1378–84.

    Article  CAS  PubMed  Google Scholar 

  40. Liao Y, Takashima S, Zhao H, Asano Y, Shintani Y, Minamino T, et al. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Cardiovasc Res. 2006;70(1):107–16.

    Article  CAS  PubMed  Google Scholar 

  41. Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, et al. Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation. 2009;119(19):2568–77.

    Article  CAS  PubMed  Google Scholar 

  42. Kim J, Nakatani S, Hashimura K, Komamura K, Kanzaki H, Asakura M, et al. Abnormal glucose tolerance contributes to the progression of chronic heart failure in patients with dilated cardiomyopathy. Hypertens Res. 2006;29(10):775–82.

    Article  CAS  PubMed  Google Scholar 

  43. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–16.

    Article  CAS  PubMed  Google Scholar 

  44. Wong M, Staszewsky L, Latini R, Barlera S, Volpi A, Chiang YT, et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study. J Am Coll Cardiol. 2002;40:970–5.

    Article  CAS  PubMed  Google Scholar 

  45. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.

    Article  CAS  PubMed  Google Scholar 

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Conflict of Interest

We declare that none of the authors of the present manuscript has a conflict of interest associated with pharmaceutical companies or third parties.

Funding

This work was supported by a Grant-in-aids from the Japanese Ministry of Health, Labor, and Welfare (H23-Nanchi-Ippan-22 to M.K.).

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Correspondence to Masafumi Kitakaze.

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Kitakaze, M., Asakura, M., Nakano, A. et al. Data Mining as a Powerful Tool for Creating Novel Drugs in Cardiovascular Medicine: The Importance of a “Back-and-Forth Loop” Between Clinical Data and Basic Research. Cardiovasc Drugs Ther 29, 309–315 (2015). https://doi.org/10.1007/s10557-015-6602-9

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  • DOI: https://doi.org/10.1007/s10557-015-6602-9

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