Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

Human monocyte transcriptional profiling identifies IL-18 receptor accessory protein and lactoferrin as novel immune targets in hypertension.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: Wiley Country of Publication: England NLM ID: 7502536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5381 (Electronic) Linking ISSN: 00071188 NLM ISO Abbreviation: Br J Pharmacol Subsets: MEDLINE
    • بيانات النشر:
      Publication: London : Wiley
      Original Publication: London, Macmillian Journals Ltd.
    • الموضوع:
      Antihypertensive Agents/*pharmacology ; Hypertension/*drug therapy ; Lactoferrin/*pharmacology ; Monocytes/*metabolism ; Receptors, Interleukin-18/*genetics; Black or African American ; Blood Pressure/drug effects ; Blood Pressure/immunology ; Case-Control Studies ; Gene Expression Profiling ; Humans ; Hypertension/immunology ; Multivariate Analysis ; Receptors, Interleukin-18/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, RNA
    • نبذة مختصرة :
      Background and Purpose: Monocytes play a critical role in hypertension. The purpose of our study was to use an unbiased approach to determine whether hypertensive individuals on conventional therapy exhibit an altered monocyte gene expression profile and to perform validation studies of selected genes to identify novel therapeutic targets for hypertension.
      Experimental Approach: Next generation RNA sequencing identified differentially expressed genes in a small discovery cohort of normotensive and hypertensive individuals. Several of these genes were further investigated for association with hypertension in multiple validation cohorts using qRT-PCR, regression analysis, phenome-wide association study and case-control analysis of a missense polymorphism.
      Key Results: We identified 60 genes that were significantly differentially expressed in hypertensive monocytes, many of which are related to IL-1β. Uni- and multivariate regression analyses of the expression of these genes with mean arterial pressure (MAP) revealed four genes that significantly correlated with MAP in normotensive and/or hypertensive individuals. Of these, lactoferrin (LTF), peptidoglycan recognition protein 1 and IL-18 receptor accessory protein (IL18RAP) remained significantly elevated in peripheral monocytes of hypertensive individuals in a separate validation cohort. Interestingly, IL18RAP expression associated with MAP in a cohort of African Americans. Furthermore, homozygosity for a missense single nucleotide polymorphism in LTF that decreases antimicrobial function and increases protein levels (rs1126478) was over-represented in patients with hypertension relative to controls (odds ratio 1.16).
      Conclusions and Implications: These data demonstrate that monocytes exhibit enhanced pro-inflammatory gene expression in hypertensive individuals and identify IL18RAP and LTF as potential novel mediators of human hypertension.
      Linked Articles: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.
      (© 2018 The British Pharmacological Society.)
    • References:
      J Am Med Inform Assoc. 2017 Jan;24(1):162-171. (PMID: 27497800)
      FASEB J. 2008 Aug;22(8):2747-57. (PMID: 18364398)
      Bioinformatics. 2010 May 1;26(9):1205-10. (PMID: 20335276)
      Br J Pharmacol. 2015 Jul;172(14):3461-71. (PMID: 26114403)
      Arterioscler Thromb Vasc Biol. 2005 May;25(5):1051-6. (PMID: 15731495)
      Circ Res. 2015 Mar 13;116(6):1022-33. (PMID: 25767287)
      ScientificWorldJournal. 2014 Jan 08;2014:768237. (PMID: 24526921)
      J Am Med Inform Assoc. 2012 Mar-Apr;19(2):212-8. (PMID: 22101970)
      Hypertens Res. 2013 Jun;36(6):496-503. (PMID: 23364341)
      PLoS One. 2012;7(3):e32628. (PMID: 22438881)
      Am J Hypertens. 2007 Apr;20(4):370-7. (PMID: 17386342)
      Front Immunol. 2017 Nov 06;8:1438. (PMID: 29163511)
      Front Genet. 2013 May 29;4:98. (PMID: 23755071)
      J Hypertens. 2007 Mar;25(3):517-23. (PMID: 17278966)
      Br J Pharmacol. 2016 Feb;173(4):752-65. (PMID: 26103560)
      Circulation. 2011 Sep 20;124(12):1370-81. (PMID: 21875910)
      Bioinformatics. 2010 Feb 15;26(4):493-500. (PMID: 20022975)
      Mol Immunol. 2009 May;46(8-9):1867-77. (PMID: 19299019)
      J Cell Sci. 2017 Dec 1;130(23):3955-3963. (PMID: 29196474)
      J Clin Invest. 2015 Mar 2;125(3):1189-202. (PMID: 25664851)
      Hypertension. 2016 Jul;68(1):167-74. (PMID: 27141060)
      J Immunol. 2015 Feb 15;194(4):1417-21. (PMID: 25595774)
      Nucleic Acids Res. 2018 Jan 4;46(D1):D1091-D1106. (PMID: 29149325)
      Br J Pharmacol. 2017 Dec;174 Suppl 1:S272-S359. (PMID: 29055034)
      BMJ Open. 2017 Nov 15;7(11):e017875. (PMID: 29146643)
      J Clin Invest. 2014 Oct;124(10):4642-56. (PMID: 25244096)
      J Exp Med. 2016 Mar 7;213(3):337-54. (PMID: 26926996)
      Pharmacol Res. 2017 Feb;116:77-86. (PMID: 27986554)
      Clin Chem. 2008 Feb;54(2):301-9. (PMID: 18156281)
      N Engl J Med. 2017 Sep 21;377(12):1119-1131. (PMID: 28845751)
      Infect Immun. 2013 May;81(5):1596-605. (PMID: 23460521)
      Cytokine. 2004 Jan 7;25(1):36-44. (PMID: 14687584)
      Int J Mol Sci. 2017 Sep 15;18(9):. (PMID: 28914813)
      PLoS One. 2013 Apr 04;8(4):e60332. (PMID: 23593194)
      Hypertension. 1999 Jul;34(1):113-7. (PMID: 10406833)
      Atherosclerosis. 2009 Apr;203(2):569-75. (PMID: 18774573)
      Clin Pharmacol Ther. 2008 Sep;84(3):362-9. (PMID: 18500243)
      J Immunol. 2017 Apr 1;198(7):2834-2843. (PMID: 28193827)
      Cell Metab. 2016 Feb 9;23(2):360-8. (PMID: 26712462)
      Biometals. 2010 Jun;23(3):365-76. (PMID: 20143251)
      PLoS One. 2017 Jul 7;12(7):e0175508. (PMID: 28686612)
      Prenat Diagn. 2009 Nov;29(11):1038-44. (PMID: 19731222)
      Jpn J Cancer Res. 2000 Oct;91(10):1022-7. (PMID: 11050473)
      Br J Pharmacol. 2017 Dec;174 Suppl 1:S17-S129. (PMID: 29055040)
      Am J Hypertens. 2004 Jun;17(6):489-94. (PMID: 15177520)
      Blood. 2003 Jul 15;102(2):689-97. (PMID: 12649138)
      Pflugers Arch. 2017 Apr;469(3-4):419-430. (PMID: 28251313)
      Br J Pharmacol. 2019 Jun;176(12):2015-2027. (PMID: 29774543)
      PLoS One. 2017 Dec 5;12(12):e0187290. (PMID: 29206834)
      Br J Pharmacol. 2014 Dec;171(24):5589-602. (PMID: 25117218)
      Hum Immunol. 2012 May;73(5):554-9. (PMID: 22406253)
      Br J Pharmacol. 2017 Dec;174 Suppl 1:S225-S271. (PMID: 29055036)
      Atherosclerosis. 2001 Jul;157(1):151-60. (PMID: 11427215)
    • Grant Information:
      F31 HL127986 United States HL NHLBI NIH HHS; K08 HL121671 United States HL NHLBI NIH HHS; R01 LM010685 United States LM NLM NIH HHS; U01 HG004603 United States HG NHGRI NIH HHS; K01 HL121045 United States HL NHLBI NIH HHS; R25 GM062459 United States GM NIGMS NIH HHS; DP2 HL137166 United States HL NHLBI NIH HHS; T32 HL007411 United States HL NHLBI NIH HHS; RC2 GM092618 United States GM NIGMS NIH HHS; T32 HL069765 United States HL NHLBI NIH HHS
    • الرقم المعرف:
      0 (Antihypertensive Agents)
      0 (Receptors, Interleukin-18)
      EC 3.4.21.- (Lactoferrin)
    • الموضوع:
      Date Created: 20180519 Date Completed: 20200731 Latest Revision: 20221207
    • الموضوع:
      20231215
    • الرقم المعرف:
      PMC6534784
    • الرقم المعرف:
      10.1111/bph.14364
    • الرقم المعرف:
      29774543