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1. Rossaak JI, van Rij AM, Jones GT, and Harris EL. Association
of the 4G/5G polymorphism in the promoter region of PAI-1 with
abdominal aortic aneurysm. J Vasc Surg 2000;31:1026-32.
Brief summary: Previous work from the Tilson laboratory and others
has implicated plasmin as a possible activator of matrix metallo-
proteases with the capacity to degrade collagen and elastin during
the growth of a AAA. Plasmin activation is regulated by PAI-1,
and a polymorphism within the PAI-1 promoter has been described
that regulates PAI-1 expression (the 4 and 5G variants). Compared
to the 5G variant, 4G increases PAI-1 expression, and consequently
might reduce plasmin activity. The authors predict that the 4G
variant would be a negative risk factor for AAA.
190 AAA patients were studied, among whom 39 familial cases,
along with 163 control patients. The ratio of 4G/5G was 6/4 in
AAA/control. 26% of familial patients were homozygous for 5G,
compared to 13% of controls.
Comment by mdt: Very interesting. Although larger #'s would be
needed to show impressive statistical significance, the results
may have substantial biological significance. Congratulations to
the authors.
2. Rowe VL and others, including MH Goldman. Vascular SMC
apoptosis in aneurysmal, occlusive, and normal human aortas.
J Vasc Surg 2000, 31: 567-76.
Brief summary: 17 AAA, 10 OCC, and 5 NOR aortas were
evaluated for SMC density and markers for apoptosis. Somewhat
surprisingly, there was not a great difference in density of SMC's:
271/HPF in AAA, 278/HPF in OCC, and 291/HPF in NOR.
However, VSMC apoptosis was greatest in AAA (11.7/HPF),
versus OCC (3.3/HPF) and NOR (3.8/HPF).
Comment by mdt: Nice work. I guess it is not too surprising, as
we showed several years ago that SMCs are expressing HLA-DR
antigens in AAA; and it is possible that these antigens might
initiate apoptotic pathways.
I'll do two more fairly basic papers this month, and then we'll get
on next month to some recent communications re endovascular
repair.
3. Curci JA and others, including BG Rubin, JM Reilly, and GA
Sicard. Preoperative treatment with doxycycline reduces aortic
wall expression and activation of MMP's in patients with AAA.
J Vasc Surg 2000; 31: 325-42.
Brief summary: AAA specimens were studied from 15 patients
who needed surgical repair. Eight took DOX prior to surgery
in a dose of 100mg PO BID x7. Differences in total MMP activity
and MMP-2 activity were unimpressive, but MMP-9 activity was
reduced 2.5x; and its mRNA was reduced five-fold.
Comment by mdt: The Wash U St. Louis group continues to make
important contributions to the field of MMP inhibition as a practical
approach to reducing the growth rate of small AAA's. When Jeff
Reilly was in my lab at Yale in 1988, I believe he was the first to
show that the "killer elastase", as we called it, was a large MMP.
Later, our lab eventually reported that antibody against MMP-9
substantially inhibited the proteolytic activity of extracts from AAA
specimens.
4. Raghavan ML and others, incl David Vorp and Marshall Webster
Wall stress distribution on 3_D reconstructed models of human AAA. J
Vasc Surg 2000; 31: 760-9.
Comment by mdt: The Pittsburgh group continues to pioneer in the
field of biomechanical modeling of the distribution of wall stresses
in the clinical AAA using computationally intense mathematical models.
The math goes over my head, but the finding that stresses are not
uniformly distributed lays a foundation, as they conclude, for more
sophisticated estimation of risk of rupture for an individual patient
than the standard of size alone.