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There has been rapid growth in interest in the etiology
of the AAA worldwide, as evidenced by the five
abstracts I have chosen to summarize this month, from
the Annual Meeting of the International Society for
Cardiovascular Surgery, which was held in September
1999 in Melbourne, Australia.
#1. YV Bobryshev, RSA Lord (Darlinghurst NSW,
Australia). Recognition of Vascular Associated
Lymphoid Tissue (VALT) involvement in aortic aneurysm.
CV Surgery vol 7, Sept 99, p. 91.
Brief summary of abstract: Vascular associated
lymphoid tissue (VALT) has recently been recognized as
the vessel analog to mucosa associated lymphoid tissue
(MALT). Here the authors describe VALT and the newly
discovered vascular dendritic cells (VDC's) in
specimens from 31 infrarenal aneurysms. In addition to
confirming observations previously made in the
laboratories of Pearce (Northwestern) and Tilson
(Columbia) regarding the prevalence of inflammatory
infiltrates mostly in adventitia (involving T cells
with CD4+ and CD8+ subsets, and B-cells). All aneurysm
walls contained S-100+ VDC's. Lymph nodule-like
structures with B-cells forming peudo-germinal centers
were seen in three specimens. "This is the first
report of VALT activation in aneurysm formation."
Comment by mdt: Well, not exactly. Brophy with Tilson
published a photomicrograph of a lymph "nodule" in the
wall of a AAA specimen almost 10 years ago (Ann Vasc
Surg (1991) 5: 229-233, Figure 1). However, Lord and
colleagues certainly deserve credit for focusing
attention on the possible key role of the vascular
dendritic cell.
#2. TWG Carrell, A Smith, KG Burnand (London, UK).
Fibrinolytic and MMP-9 activity in the intraluminal
thrombus of AAA. (op site, page 90).
Brief Summary of Abstract: The activities of tPA, uPA,
and MMP-9 were measured in extracts of AAA wall,
organized juxtamural thrombus, and fresh intralminal
thrombus. Mural tPA & uPA were higher than levels
measured in old or fresh thrombus; but MMP-9 activity
was elevated in all.
Comment by mdt: Well, I guess that disposes of a
notion that was speculated several years ago, namely
that fibrinolytic enzymes which are activators of the
MMP family might be leaching into the wall from the
juxtamural thrombus. Congratulations to the authors.
3. M Ikebuchi, K Nishimura, T Maeda, T Hiroe, M
Tachibana, S Ohgi. Producibility of MMP-9 in the AAA
wall. (op cit, p 87)
Brief summary of abstract: The authors confirm that
MMP-9 is elevated in conditioned medium of cells
cultured from AAA, with highest levels being measured
in AAAs of moderate diameter. In the largest AAA's,
levels declined significantly with respect to the
moderate group. COPD and hypercholesterolemia were
considered to be promoting factors of MMP-9 production.
The authors conclude that "degenerate change due to
over-expression of MMP-9 is considered to be associated
with the aortic expansion mainly in moderate AAA,
however, hemodynamic factors may be more important in
large aneurysms."
Comment by mdt: Interesting.
4. WF Oppat, AC Chiou, WD McMillan, RL Chisholm, WH
Pearce. Does MMP-9 over-expression cause aortic
aneurysms? (op cit, p. 87)
Brief summary of abstract: Pearce and coworkers raise
the question whether the over-expression of MMPs in
AAA wall is only an incidental finding in AAA or a "key
player in the pathogenesis of aneurysm formation". To
study this question, they have coupled an aortic SMC
cell-specific promoter (SM22 slpha) to an expressing
MMP-9 gene in a transgenic mouse. By Southern blot, 6
of 39 founder mice had incorporated the construct into
their genome, and overexpression of MMP-9 was
demonstrated by zymography in aortic tissue of the
transgenic mice compared to non-transgene littermates.
Brief comment by mdt: WOW! Congratulations to the
Pearce group for this first (to the best of my
knowledge) application of modern molecular transgenics
to study the AAA problem. It will certainly be
interesting to see whether the transgenics eventually
get aneurysms without further manipulations.
5. RW Schutzer, YA Gabriel, K Hardy, S Xia, MD Tilson.
Localization of fibrillin in aortic adventitia may
explain the development of aneurysms in patients with
Marfan syndrome. (op cite, page 67).
Brief comment by mdt: This was a little contribution
from my own lab. I have never understood why patients
with Marfan get thoracic aneurysms, since their
mutation in fibrillin-1 (FBN-1) should be associated
with abnormalities in the deposition of tropoelastin,
or other defects in elastin organization. I have made
the argument many times before that elastin failure is
insufficient to cause aortic dilatation to aneurysmal
dimensions, because of the load-bearing collagen in the
adventitial layer. Accordingly, my research fellow
Rich Schutzer took an interest in this enigmatic
phenomenon; and to our surprise, he found that antibody
to FBN-1 co-distributes conspicuously with fibrils of
Type I and III collagen in the aortic adventitia. Good
work, Rich. Let's move on to work on other problems.
The hard-core chemists should have fun figuring out the
intermolecular interaction of fibrillin with collagens
and additional structural elements.