Up-regulation and coexpression of MIF and matrix metalloproteinases in human abdominal aortic aneurysms
article
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. © Mary Ann Liebert, Inc. Chemicals / CAS: gelatinase B, 146480-36-6; interstitial collagenase, 9001-12-1; Macrophage Migration-Inhibitory Factors; Matrix Metalloproteinase 1, EC 3.4.24.7; Matrix Metalloproteinase 12, EC 3.4.24.65; Matrix Metalloproteinase 9, EC 3.4.24.35; Metalloendopeptidases, EC 3.4.24.-; MMP12 protein, human, EC 3.4.24.65; Nucleic Acids; RNA, Messenger
Topics
Biomedical Researchgelatinase Binterstitial collagenasemacrophage elastasemacrophage migration inhibition factormatrix metalloproteinaseabdominal aorta aneurysmaorta wallartery dilatationatherosclerosiscellular distributioncytotoxicityendothelium cellhumanhuman tissueimmunohistochemistrymacrophagemortalitypathogenesispriority journalprotein expressionprotein localizationprotein structuresmooth muscle fiberT lymphocyteupregulationAortaAortic Aneurysm, AbdominalBlotting, WesternGene Expression RegulationHumansImmunohistochemistryInflammationMacrophage Migration-Inhibitory FactorsMacrophagesMatrix Metalloproteinase 1Matrix Metalloproteinase 12Matrix Metalloproteinase 9MetalloendopeptidasesMyocytes, Smooth MuscleNucleic AcidsReverse Transcriptase Polymerase Chain ReactionRNA, MessengerT-LymphocytesT-Lymphocytes, CytotoxicUp-Regulation
TNO Identifier
238682
ISSN
15230864
Source
Antioxidants and Redox Signaling, 7(9-10), pp. 1195-1202.
Pages
1195-1202
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