Article (Scientific journals)
TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas.
Defawe, Olivier D; Colige, Alain; Lambert, Charles et al.
2003In Cardiovascular Research, 60 (1), p. 205-13
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Keywords :
Aged; Aged, 80 and over; Analysis of Variance; Aorta, Abdominal/metabolism; Aortic Aneurysm/metabolism; Arteriosclerosis/metabolism; Case-Control Studies; Extracellular Matrix Proteins/metabolism; Humans; Middle Aged; Peptide Hydrolases/metabolism; Plasminogen Activator Inhibitor 1/genetics; RNA, Messenger/analysis; Reverse Transcriptase Polymerase Chain Reaction; Tissue Inhibitor of Metalloproteinase-2/genetics
Abstract :
[en] OBJECTIVE: Significant alterations of the vascular wall occurs in abdominal aortic aneurysm (AAA) and atherosclerotic occlusive disease (AOD) that ultimately may lead to either vascular rupture or obstruction. These modifications have been ascribed to one or a group of proteases, their inhibitors or to the matrix macromolecules involved in the repair process without considering the extent of the observed variations. METHODS: The mRNA steady-state level of a large spectrum of proteolytic enzymes (matrix metalloproteinases: MMP-1, -2, -3, -8, -9, -11, -12, -13, -14; urokinase plasminogen activator: u-PA), their physiological inhibitors (tissue inhibitors of MMPs: TIMP-1, -2, -3; plasminogen activator inhibitor: PAI-1) and that of structural matrix proteins (collagens type I and III, decorin, elastin, fibrillins 1 and 2) was determined by RT-PCR made quantitative by using a synthetic RNA as internal standard in each reaction mixture. The profile of expression was evaluated in AAA (n=7) and AOD (n=5) and compared to non-diseased abdominal (CAA, n=7) and thoracic aorta (CTA, n=5). RESULTS: The MMPs -8, -9, -12 and -13 mostly associated with inflammatory cells were not or barely detected in CAA and CTA while they were largely and similarly expressed in AAA and AOD. Expression of protease inhibitors or structural proteins were only slightly increased in both pathological conditions with the exception of elastin which was reduced. The main significant difference between AAA and AOD was a lower expression of TIMP-2 and PAI-1 in the aneurysmal lesions. CONCLUSIONS: The remodeling of the aortic wall in AAA and AOD involves gene activation of a large and similar spectrum of proteolytic enzymes while the expression of two physiological inhibitors, TIMP-2 and PAI-1, is significantly lower in AAA compared to AOD. The repair process in the aneurysmal disease seems similar to that of the occlusive disease.
Disciplines :
Biochemistry, biophysics & molecular biology
Surgery
Author, co-author :
Defawe, Olivier D;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des Tissus Conjonctifs
Colige, Alain ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des Tissus Conjonctifs
Lambert, Charles ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des Tissus Conjonctifs
Munaut, Carine  ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Delvenne, Philippe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Lapiere, Charles M
Limet, Raymond ;  Université de Liège - ULiège > Département des sciences cliniques > Chirurgie Cardio-vasculaire et thoracique - CHU
Nusgens, Betty ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de Biologie des Tissus Conjonctifs
SakalihasanN, Natzi ;  Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Language :
English
Title :
TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas.
Publication date :
2003
Journal title :
Cardiovascular Research
ISSN :
0008-6363
eISSN :
1755-3245
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
60
Issue :
1
Pages :
205-13
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 25 May 2010

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