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Up-regulation and coexpression of MIF and matrix metalloproteinases in human abdominal aortic aneurysms.
- Source :
-
Antioxidants & redox signaling [Antioxid Redox Signal] 2005 Sep-Oct; Vol. 7 (9-10), pp. 1195-202. - Publication Year :
- 2005
-
Abstract
- Abdominal aortic aneurysm (AAA) is a localized dilatation of the arterial wall as a result of extensive breakdown of its structural proteins by matrix metalloproteinases (MMPs). AAA continuously expand and may eventually rupture, causing high mortality rates. The molecular processes underlying expansion and rupture of AAA are only poorly understood. In this study, evidence was sought for a direct involvement of macrophage migration inhibitory factor (MIF) in the pathogenesis of AAA through up-regulating MMPs, with particular reference to macrophages. To this end, expression and cellular localization of MIF were analyzed in human aortic wall samples of stable AAA and ruptured AAA, and compared with control aorta and atherosclerotic aorta (AS). MIF expression was up-regulated in stable AAA and further intensified in ruptured AAA. The increased aneurysmal MIF expression was paralleled by an enhanced expression of specific MMPs, viz. MMP-1, MMP-9, and MMP-12, and by a decrease of their inhibitors. Immunohistochemical analysis of AAA and AS showed MIF protein in endothelial cells, smooth muscle cells (SMCs), macrophages, and T cells. MMP-1 (in SMCs and macrophages) and MMP-9 (in macrophages) were colocalized with MIF at the cellular level in ruptured AAA. The up-regulation of aneurysmal MIF/MMP expression was associated with an increased content of cytotoxic T cells.
- Subjects :
- Aorta metabolism
Aorta pathology
Blotting, Western
Gene Expression Regulation
Humans
Immunohistochemistry
Inflammation
Macrophages cytology
Matrix Metalloproteinase 1 biosynthesis
Matrix Metalloproteinase 12
Matrix Metalloproteinase 9 biosynthesis
Metalloendopeptidases biosynthesis
Myocytes, Smooth Muscle cytology
Nucleic Acids chemistry
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes cytology
T-Lymphocytes metabolism
T-Lymphocytes, Cytotoxic cytology
Aortic Aneurysm, Abdominal metabolism
Aortic Aneurysm, Abdominal pathology
Macrophage Migration-Inhibitory Factors biosynthesis
Up-Regulation
Subjects
Details
- Language :
- English
- ISSN :
- 1523-0864
- Volume :
- 7
- Issue :
- 9-10
- Database :
- MEDLINE
- Journal :
- Antioxidants & redox signaling
- Publication Type :
- Academic Journal
- Accession number :
- 16115023
- Full Text :
- https://doi.org/10.1089/ars.2005.7.1195