TIMP-2 and PAI-1 mRNA levels are lower in aneurysmal as compared to athero-occlusive abdominal aortas.
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.
Defawe
Olivier D
OD
Laboratory of Connective Tissues Biology, Tour de Pathologie B23/3, CHU Sart-Tilman, University of Liège, Liège, 4000, Belgium. lctb@ulg.ac.be
Colige
Alain
A
Lambert
Charles A
CA
Munaut
Carine
C
Delvenne
Philippe
P
Lapière
Charles M
CM
Limet
Raymond
R
Nusgens
Betty V
BV
Sakalihasan
Natzi
N
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001012:Aorta, Abdominal / Q000378:metabolism*; D001014:Aortic Aneurysm / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D016326:Extracellular Matrix Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D010447:Peptide Hydrolases