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  • Sun, J.Harvard Medical School, Boston, MA, USA (author)

Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation

  • Article/chapterEnglish2009

Publisher, publication year, extent ...

  • 2009
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-109529
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-109529URI
  • https://doi.org/10.1161/CIRCULATIONAHA.109.849679DOI
  • https://res.slu.se/id/publ/28024URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Mast cell chymase may participate in the pathogenesis of human abdominal aortic aneurysm (AAA), yet a direct contribution of this serine protease to AAA formation remains unknown. METHODS AND RESULTS: Human AAA lesions had high numbers of chymase-immunoreactive mast cells. Serum chymase level correlated with AAA growth rate (P=0.009) in a prospective clinical study. In experimental AAA produced by aortic elastase perfusion in wild-type (WT) mice or those deficient in the chymase ortholog mouse mast cell protease-4 (mMCP-4) or deficient in mMCP-5 (Mcpt4(-/-), Mcpt5(-/-)), Mcpt4(-/-) but not Mcpt5(-/-) had reduced AAA formation 14 days after elastase perfusion. Even 8 weeks after perfusion, aortic expansion in Mcpt4(-/-) mice fell by 50% compared with that of the WT mice (P=0.0003). AAA lesions in Mcpt4(-/-) mice had fewer inflammatory cells and less apoptosis, angiogenesis, and elastin fragmentation than those of WT mice. Although Kit(W-sh/W-sh) mice had protection from AAA formation, reconstitution with mast cells from WT mice, but not those from Mcpt4(-/-) mice, partially restored the AAA phenotype. Mechanistic studies suggested that mMCP-4 regulates expression and activation of cysteine protease cathepsins, elastin degradation, angiogenesis, and vascular cell apoptosis. CONCLUSIONS: High chymase-positive mast cell content in human AAA lesions, greatly reduced AAA formation in Mcpt4(-/-) mice, and significant correlation of serum chymase levels with human AAA expansion rate suggests participation of mast cell chymase in the progression of human and mouse AAA.

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Zhang, J.Harvard Medical School, Boston, MA, USA (author)
  • Lindholt, J.S.Harvard Medical School, Boston, MA, USA (author)
  • Sukhova, G.K.Harvard Medical School, Boston, MA, USA (author)
  • Liu, J.Harvard Medical School, Boston, MA, USA (author)
  • He, A.Harvard Medical School, Boston, MA, USA (author)
  • Åbrink, Magnus,1964-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Uppsala University(Swepub:slu)48145 (author)
  • Pejler, GunnarSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för molekylär biovetenskap,Department of Molecular Biosciences,Sectionen för biokemi, AFB, SLU, Uppsala,Harvard Medical School, Boston, MA, USA(Swepub:slu)49530 (author)
  • Stevens, R.L.Harvard Medical School, Boston, MA, USA (author)
  • Thompson, R.W.Harvard Medical School, Boston, MA, USA (author)
  • Ennis, T.L.Harvard Medical School, Boston, MA, USA (author)
  • Gurish, M.F.Harvard Medical School, Boston, MA, USA (author)
  • Libby, P.Harvard Medical School, Boston, MA, USA (author)
  • Shi, G.P.Harvard Medical School, Boston, MA, USA (author)
  • Harvard Medical School, Boston, MA, USAInstitutionen för medicinsk biokemi och mikrobiologi (creator_code:org_t)
  • Sveriges lantbruksuniversitet

Related titles

  • In:Circulation120:11, s. 973-9820009-73221524-4539

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