Enhanced expression of matrix metalloproteinase-9 in abdominal aortic aneurysms.
Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n = 8), atherosclerotic occlusive diseases (AOD) (n = 8), and normal subjects (n = 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.
Yamashita
A
A
Department of Biochemistry, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Noma
T
T
Nakazawa
A
A
Saito
S
S
Fujioka
K
K
Zempo
N
N
Esato
K
K
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9