Papers of the Month - Jul 96

1. Sakalihasan N, Delvenne P, Nusgens BV, Limet R,
Lapiere CM.  Activated forms of MMP-2 and MMP-9 in AAA's. 
JVS 1996; 24: 127-33.

Purpose: Consistent observations of reduced elastin
content in AAA led the authors to study two MMP's (2 & 9)
that have elastolytic activity.

Methods: Substrate gel zymography on serum & tissue
extracts from 10 AAA patients & 6 age-matched controls,
plus semiquantitative morphometrics to score inflammatory
infiltrate in aortic tissues.

Results: Increased MMP-9 in AAA wall, much of which was
in its activated form (which was never observed in
control samples).  Also a higher proportion of MMP-2 in
active form in AAA tissue, which correlated positively
with the inflammatory score.

Conclusion: MMP's 2 & 9 may contribute to degradation of
ECM during AAA development. 


Comment by mdt: Yes, several other studies have pointed
in this direction.


2. Patel MI, Melrose J, Ghosh P, Appleberg M.  Increased
synthesis of matrix metalloproteinases by aortic smooth
muscle cells is implicated in the etiopathogenesis of
AAA.  J Vasc Surg 1996; 24:82-92.

Purpose: To identify the MMP's elaborated by AAA SMC's in
monolayers cultured from the outgrowth cells of tunica
media explants.

Methods: Identity of SMC's confirmed by staining with
anti-SMC alpha-actin antibody.  MMP production evaluated
by gelatin zymography and Western blots with monoclonal
antibodies to MMP-2, 3, and 9.

Results:  More proteolytic activity detected in serum-
free CM from AAA explants than control explants. 
Zymography established MW's of metal-dependent
gelatinases at 50-64 and 92 kDa, identified respectively
as MMP-2 and MMP-9.

Conclusion:  "SMC's mayh be involved in the abnormal
degradation of the aortic wall in AAA through the
excessive MMP activity produced."


Comment by mdt:  Interesting...   In our reported work on
the immunohistochemical localization of MMP's in the AAA
wall (JVS 1994; 20:814-20), we found that the macrophage
was the principal producer of MMP-9, while MMP-1 appeared
to arise from the mesenchymal and endothelial cells.  Of
course, that doesn't mean that once SMC's are freed of
their in-vivo constraints and grown in tissue culture
that they shouldn't (or couldn't) start making MMP-9.

3. Hunter GC, Smyth SH, Aguirre ML, Baxter BT, Bull DA,
King DD, Wang YP, Hall KA, Putnam CW.  Incidence and
histological characteristics of blebs in patients with
AAA's.  J Vasc Surg 1996; 24: 93-101.

Purpose: As stated in title.

Methods: 188 CT scans of AAA's evaluated for presence,
location, and size of detected blebs.  16 blebs in
surgical specimens evaluated by light microscopy and
immunohistochemistry.  

Results: 20 blebs averaging 12 mm in size detected in 11%
of the CT scans.  Large AAA's (>7 cm) had a higher
incidence (19%, 3 of 16 patients).  Histologically, the
typical inflammatory infiltrate was detected in the
adventitia of the AAA's, but involved both the media and
the adventitia of the blebs.  Further study by in-situ
hybridization demonstrated alpha-1 (I) procollagen mRNA
in 4 of 5 AAA specimens, compared with only one of 6
blebs.

Conclusion: Attenuation of the aortic wall accompanying
the formation of blebs may predispose these sites to
rupture.


Comment by mdt: I have been following Dr. Hunter's work
on the role of blebs in aneurysm rupture with interest. 
Perhaps the presence of a bleb on a small AAA might push
one toward recommending an earlier repair than usual, all
other things being equal.


4. Schwartz LB, Belkin M, Donaldson MC, Mannick JA,
Whittemore AD.  Improvement in results of repair of type
IV thoracoabdominal aortic aneurysms.  JVS 1996; 24: 74-
81.


Comment by mdt: The title pretty much says it all, so I
won't reiterate all of the detail.  To summarize briefly,
the in-hospital mortality decreased from 39% between
1977-1987 to 2% between 1988-1994.  This is an
*impressive* result from a first-class surgical group.