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International Angiology 2003 September;22(3):229-38


lingua: Inglese

Relationships between Matrix metalloproteinases and tissue inhibitor of metalloproteinases in the wall of abdominal aortic aneurysms

Nishimura K. 1, Ikebuchi M. 1, Kanaoka Y. 1, Ohgi S. 1, Ueta E. 2, Nanba E. 2, Ito H. 3

1 Second Department of Surgery, Tottori University Faculty of Medicine, Tottori, Japan 2 Gene Research Center, Tottori University, Tottori, Japan 3 First Department of Pathology, Tottori University Faculty of Medicine, Tottori, Japan


Aim. The path­o­log­ic fea­ture of aor­tic aneu­rysm is con­sid­ered to be the remod­el­ing of the aor­tic wall, involv­ing frag­men­ta­tion and ­decrease of elas­tic ­fibers in the tuni­ca media. ­Matrix met­al­lop­ro­tei­nas­es (MMPs), par­tic­u­lar­ly MMP-2 and MMP-9, have been impli­cat­ed in col­la­gen and elas­tin degen­er­a­tion with­in the aor­tic wall. The pre­cise rela­tion­ship among MMPs and tis­sue inhib­i­tor of met­al­lop­ro­tei­nas­es (TIMPs) is still ­unclear. We have stud­ied the expres­sion of MMP-2, MMP-9 tis­sue inhib­i­tor of met­al­lo­pro­tein-1 (TIMP-1), TIMP-2 and mem­brane type 1-MMP (MT-1-MMP) in the wall of small AAAs (30-45 mm), large AAAs (>45 mm) and con­trols (<25 mm). We inves­ti­gat­ed the rela­tion­ship among expres­sions of MMP-2, TIMP-2 and MT1-MMP in the walls.
Meth­ods. The aor­tic walls in the ­patients with AAA were har­vest­ed from the max­i­mum diam­e­ter, while the aor­tic walls in autop­sy cas­es were har­vest­ed as con­trols. We ana­lyzed tis­sue dis­tri­bu­tion of cell types by immu­no­chem­is­try, pro­tein expres­sion by West­ern blot­ting and mRNA expres­sion by com­pet­i­tive poly­me­rase chain reac­tion.
­Results. They con­sist­ed of 11 in con­trols, 8 in small AAAs and 26 in large AAAs. Among the MMPs-pos­i­tive-cells, main­ly mac­ro­phage, MMP-2-pos­i­tive cells were in the inti­ma, but MMP-9-pos­i­tive cells in the inti­ma and adven­ti­tia. In the small size, MMP-2 and MMP-9 mRNA were high­er than those of con­trol. In the large size, MT1-MMP and MMP-9 mRNA were high­er than those of the con­trols. In the mRNA level of the whole AAA, sig­nif­i­cant cor­re­la­tions were ­present ­between MMP-2 and MMP-9, ­between MMP-2 and TIMP-1, and between MMP-9 and TIMP-1. These expres­sions were con­firmed by West­ern blot­ting.
Con­clu­sion. We con­clud­ed as fol­lows: 1) MMP-2 and MMP-9 may play an impor­tant role in the devel­op­men­tal pro­cess of AAA. 2) TIMP-1 plays an impor­tant role of inter­act­ing MMP-2 and/or MMP-9. 3) MMP-2 and MT1-MMP may play an impor­tant role in the early stag­es of AAAs.

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