Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Cardiomyopathies*/etiology ; Cardiomyopathies*/metabolism ; Intramolecular Oxidoreductases* ; Lipocalins* ; Muscular Dystrophy, Duchenne*/genetics; Animals ; Humans ; Mice ; Disease Models, Animal ; Mast Cells/metabolism ; Mice, Inbred mdx ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Pericytes/metabolism
    • Abstract:
      The leading cause of death for patients with Duchenne muscular dystrophy (DMD), a progressive muscle disease, is heart failure. Prostaglandin (PG) D 2 , a physiologically active fatty acid, is synthesized from the precursor PGH 2 by hematopoietic prostaglandin D synthase (HPGDS). Using a DMD animal model ( mdx mice), we previously found that HPGDS expression is increased not only in injured muscle but also in the heart. Moreover, HPGDS inhibitors can slow the progression of muscle injury and cardiomyopathy. However, the location of HPGDS in the heart is still unknown. Thus, this study investigated HPGDS expression in autopsy myocardial samples from DMD patients. We confirmed the presence of fibrosis, a characteristic phenotype of DMD, in the autopsy myocardial sections. Additionally, HPGDS was expressed in mast cells, pericytes, and myeloid cells of the myocardial specimens but not in the myocardium. Compared with the non-DMD group, the DMD group showed increased HPGDS expression in mast cells and pericytes. Our findings confirm the possibility of using HPGDS inhibitor therapy to suppress PGD 2 production to treat skeletal muscle disorders and cardiomyopathy. It thus provides significant insights for developing therapeutic drugs for DMD.
    • References:
      Lancet Neurol. 2018 May;17(5):445-455. (PMID: 29398641)
      Am J Pathol. 2009 May;174(5):1735-44. (PMID: 19359520)
      Skelet Muscle. 2018 Oct 10;8(1):31. (PMID: 30305165)
      Cell Rep. 2019 Nov 12;29(7):1832-1847.e8. (PMID: 31722201)
      Cell. 2023 Dec 7;186(25):5500-5516.e21. (PMID: 38016470)
      Muscle Nerve. 2003 Oct;28(4):402-22. (PMID: 14506712)
      Sleep Med Rev. 2011 Dec;15(6):411-8. (PMID: 22024172)
      Glia. 2003 May;42(3):263-74. (PMID: 12673832)
      Acta Neuropathol. 2002 Oct;104(4):377-84. (PMID: 12200624)
      Circ Res. 2016 May 13;118(10):1563-76. (PMID: 27174950)
      J Clin Invest. 2023 May 15;133(10):. (PMID: 37183820)
      Curr Gene Ther. 2015;15(4):364-80. (PMID: 26122099)
      Cells. 2019 Jun 20;8(6):. (PMID: 31226822)
      Chem Rev. 2011 Oct 12;111(10):5821-65. (PMID: 21942677)
      Brain Dev. 2018 Nov;40(10):918-925. (PMID: 30006121)
      Science. 2015 Jan 23;347(6220):1260419. (PMID: 25613900)
      Ann Clin Transl Neurol. 2018 Oct 10;5(11):1338-1349. (PMID: 30480028)
      Lancet. 2019 Nov 30;394(10213):2025-2038. (PMID: 31789220)
      Ann Clin Transl Neurol. 2020 Feb;7(2):181-190. (PMID: 31957953)
      J Biol Chem. 1995 Aug 11;270(32):18910-6. (PMID: 7642548)
      Lancet. 2002 Feb 23;359(9307):687-95. (PMID: 11879882)
      Clin Chim Acta. 2013 Aug 23;423:10-4. (PMID: 23603101)
      Nature. 2021 Jan;589(7841):281-286. (PMID: 33176333)
      J Med Chem. 2021 Nov 11;64(21):15868-15882. (PMID: 34652145)
      Eur J Biochem. 2000 Jun;267(11):3315-22. (PMID: 10824118)
      FASEB J. 2011 Sep;25(9):3106-14. (PMID: 21665956)
      Diagnostics (Basel). 2020 Nov 26;10(12):. (PMID: 33256203)
      Adv Exp Med Biol. 2019;1122:187-210. (PMID: 30937870)
      Cell. 1987 Dec 24;51(6):919-28. (PMID: 3319190)
      Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):163-7. (PMID: 12895599)
      Nature. 2020 Nov;587(7835):555-566. (PMID: 33239795)
      Br J Pharmacol. 2008 Mar;153 Suppl 1:S191-9. (PMID: 17965752)
      Ann Neurol. 2012 Mar;71(3):304-13. (PMID: 22451200)
      Methods Mol Biol. 2018;1687:19-28. (PMID: 29067653)
      Lancet Neurol. 2010 Feb;9(2):177-89. (PMID: 19945914)
      Methods Mol Biol. 2017;1556:129-147. (PMID: 28247348)
    • Grant Information:
      21K11613 Grant-in-Aid for Scientific Research C from Japan for the Promotion of Science; JP22wm042501 Japan Agency for Medical Research and Development
    • Contributed Indexing:
      Keywords: Duchenne muscular dystrophy; hematopoietic prostaglandin D synthase; mast cell; myeloid cell; pericyte; prostaglandin D2
    • Accession Number:
      EC 5.3.- (Intramolecular Oxidoreductases)
      0 (Lipocalins)
      EC 5.3.99.2 (prostaglandin R2 D-isomerase)
      EC 5.3.99.2 (HPGDS protein, human)
    • Publication Date:
      Date Created: 20240210 Date Completed: 20240215 Latest Revision: 20240215
    • Publication Date:
      20250114
    • Accession Number:
      PMC10855661
    • Accession Number:
      10.3390/ijms25031846
    • Accession Number:
      38339125