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http://purl.uniprot.org/citations/19720934http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19720934http://www.w3.org/2000/01/rdf-schema#comment"

Background

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."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.109.849679"xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Sun J."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"He A."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Thompson R.W."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Stevens R.L."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Pejler G."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Gurish M.F."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Shi G.P."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Libby P."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Sukhova G.K."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Abrink M."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Ennis T.L."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/author"Lindholt J.S."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/pages"973-982"xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/title"Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation."xsd:string
http://purl.uniprot.org/citations/19720934http://purl.uniprot.org/core/volume"120"xsd:string
http://purl.uniprot.org/citations/19720934http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19720934
http://purl.uniprot.org/citations/19720934http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19720934
http://purl.uniprot.org/uniprot/#_A4ZVL1-mappedCitation-19720934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19720934
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