Critical Role of Mast Cell Chymase in Mouse Abdominal Aortic Aneurysm Formation
| Autor: | Jiusong Sun, Gunnar Pejler, Guo-Ping Shi, Peter Libby, Jian Liu, Michael F. Gurish, Robert W. Thompson, Jes S. Lindholt, Jie Zhang, Richard L. Stevens, Galina K. Sukhova, Terri L. Ennis, Magnus Åbrink, Aina He |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Male
Pathology Apoptosis 030204 cardiovascular system & hematology environment and public health Muscle Smooth Vascular Pathogenesis Aortic aneurysm Mice 0302 clinical medicine Mast Cells Aged 80 and over 0303 health sciences biology Serine Endopeptidases Middle Aged Mast cell Abdominal aortic aneurysm medicine.anatomical_structure cardiovascular system Female Cardiology and Cardiovascular Medicine Adult medicine.medical_specialty macromolecular substances Gene Expression Regulation Enzymologic Article 03 medical and health sciences Aneurysm Chymases Physiology (medical) medicine Animals Humans cardiovascular diseases 030304 developmental biology Aged Cathepsin Serine protease business.industry Macrophages Microcirculation Chymase medicine.disease Cathepsins Mice Mutant Strains Mice Inbred C57BL enzymes and coenzymes (carbohydrates) Disease Models Animal biology.protein business Aortic Aneurysm Abdominal |
| Zdroj: | Circulation; Vol 120 Sun, J, Zhang, J, Lindholt, J S, Sukhova, G K, Liu, J, He, A, Åbrink, M, Pejler, G, Stevens, R L, Thompson, R W, Ennis, T L, Gurish, M F, Libby, P & Shi, G-P 2009, ' Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation ', Circulation, vol. 120, no. 11, pp. 973-982 . https://doi.org/10.1161/CIRCULATIONAHA.109.849679 Sun, J, Zhang, J, Lindholt, J S, Sukhova, GK, Liu, J, He, A, Abrink, M, Pejler, G, Stevens, PL, Thompson, R W, Ennis, TL, Gurish, MF, Lippy, P & Shi, G-P 2009, ' Critical role of mast cell chymase in mouse abdominal aortic aneurysm formation ' Circulation, vol. 120, no. 11, pp. 973-82 . https://doi.org/10.1161/CIRCULATIONAHA.109.849679 |
| ISSN: | 0009-7322 |
| DOI: | 10.1161/circulationaha.109.849679 |
| Popis: | 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 notMcpt5−/−had reduced AAA formation 14 days after elastase perfusion. Even 8 weeks after perfusion, aortic expansion inMcpt4−/−mice fell by 50% compared with that of the WT mice (P=0.0003). AAA lesions inMcpt4−/−mice had fewer inflammatory cells and less apoptosis, angiogenesis, and elastin fragmentation than those of WT mice. AlthoughKitW-sh/W-shmice had protection from AAA formation, reconstitution with mast cells from WT mice, but not those fromMcpt4−/−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 inMcpt4−/−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. |
| Databáze: | OpenAIRE |
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