The Aneurysm Information Project

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    Papers of the Month - June 1998
    
    Highlights of the Soc Vasc Surg/ International Soc CV
    Surg presentations on AAA disease at the annual meeting
    in San Diego, June 7-10, 1998.
    
    1. McMillan WD, Pearce WH.  Increased plasma levels of
    MMP-9 are associated with abdominal aortic aneurysms.  
    (in man!)
    
    Shortened abstract:  Sandwich ELISA was used to measure
    plasma MMP-9 in 22 patients with AAA, 9 with AOD, and 8
    normals; and also in 48 hour supernatants from organ
    cultures.  Plasma MMP-9 was more than 3x greater in AAA
    than in AOD; and the organ culture studies suggest that
    diseased aortic tissue is the source of MMP-9.  Also,
    patients with multiple aneurysms had higher plasma levels
    than those with an isolated AAA.
    
    Comment by mdt:  I think it is accurate to say that our
    lab was the first to report that an activated form of
    MMP-9 is present in the walls of AAA specimens
    (Arterioscler Thromb 1994; 14: 1315-20); and that
    antibody against MMP-9 inhibits the most conspicuous
    gelatinase evident on substrate gel enzymography
    (purified with r-TIMP @ MW 80 kDa).  The present work is
    an important contribution, suggesting that MMP-9 escapes
    from the aneurysmal wall to circulate in plasma, where it
    may be a useful marker of proteolytic activity in the
    aneurysm.  
    
    
    2. Grange JJ, Baca-Regen LM, Lie J, Barent BL, Davis VA,
    Baxter BT.  MMP-2 expression can be regulated in human
    aortic smooth muscle cells (SMC's) by
    macrophage/lymphocyte interactions.  
    
    Short statement of principal findings:  SMC exposed to
    media from macrophages co-cultured with activated T-cells
    produced more MMP-2 than controls stimulated with media
    from either macrophages or T-cells alone.  Upregulation
    of MMP-2 by inflammatory cell coculture media was
    attenuated when the macrophages were pretreated with
    indomethacin.  
    
    Comment by mdt:  These findings are interesting and
    provide additional impetus to the notion that anti-
    inflammatory therapies, directed against MMP activities
    in particular, may be useful as a therapeutic approach to
    stabilizing the growth of small aneurysms (or perhaps
    even preventing them in people found to be genetically
    susceptible).  Work from our lab (Surgical Forum 1994;
    45: 375) suggested that extracts from aneurysmal aortas
    (which are somewhat equivalent in a clinical sense to a
    macrophage/lymphocyte co-culture) stimulated production
    of MMP-9 in a cultured macrophage-like cell line.  Baxter
    et al might find it informative to determine whether
    lymphocytes harvested from AAA specimens had greater
    stimulatory properties than lymphocytes from other
    tissues in non-AAA patients.
    
    
    3. Miralles M, Wester W, Thompson RW, Sicard GA, Reilly
    JM.  Prostaglandin E2 (PGE2) synthesis correlates with
    aneurysmal expansion of the aorta and is regulated by
    cyclooxygenase-2 (cox2).  
    Brief statement of principal findings:  The authors use
    the Anidjar/Dobrin rat model to show that AAA formation
    is associated with the production of PGE2, and that the
    synthesis of PGE2 is probably regulated by the cox2
    isoform of cycloogenase.  By in-situ hybridization, the
    source of cox2 appears to be the Aneurysm-Infiltrating-
    Macrophage (which we named the "AIM" cell in a
    communication several years ago).  This paper, as does #2
    above, points in the direction of pharmacological
    approaches to down-modulating AAA growth.  (BTW, I can't
    resist expressing satisfaction at seeing one of my former
    students, Jeff Reilly, now leading his own research
    program at Washington Univ, St. Louis; and, incidentally,
    the previous paper on the program was given by another
    former student, Colleen Brophy, who is leading a major
    research project on the biology of the vascular smooth
    muscle cell at the Medical College of Georgia.)