Aneurysm Papers of the Month - May 1995

1. Medial neovascularization in AAA: A histopathologic marker of
aneurysmal degeneration with pathophysiological implications.  DR
Holmes, S Liao, WC Parks, and RW Thompson.  J Vasc Surg  1995; 21:
761-72.

Abstract (condensed from authors): 

     Background: The purpose was to characterize the distribution
of microvessels in normal (NL), atherosclerotic (AOD), and AAA to
evaluate whether medial neovascularization (MNV) is a reliable
marker of aneurysmal degeneration.

     Methods:  9 NL, 10 AOD, and 10 AAA were examined for elastin
(EVG), an endothelial specific antigen, and laminin.  Morphometric
methods were used to evaluate results.

     Results: MNV was generally not seen in NL and AOD.  AAA
revealed strong spatial correlations between MNV, elastin
disruptions, and chronic inflammation in the outer aortic wall. 
The density of MNV was 15x higher in AAA compared with NL and 3x
higher compared with AOD.  (ANOVA, p < 0.001).

     Conclusion: MNV in AAA is a marker of aneurysmal degeneration
that is spatially correlated with the destruction of elastin and
chronic inflammation.  .......


Comment by mdt:  I think that Brophy and I were the first to point
out that MNV is a conspicuous feature of the AAA (as quoted in the
above paper) [BTW, if this is not accurate, at least in recent
times, I would like to stand corrected; use my E-mail address]. 
Anyway, Herron et al (Arterioscler Thromb 1991; 11: 1667-77)
deserve credit for postulating that the MNV should be evaluated
more carefully for a role of pathophysiological significance in AAA
development.  They found that TIMP and gelatinase-A localized to
the vasa vasorum and concluded "these results suggest the
involvement of the vasa vasorum in the maintenance and possibly the
genesis of AAA's."  The present work by Holmes et al is another
important contribution to this possibility, although it is not
clear why the authors wish to assert that AOD may extend into AAA
as if AAA were a process that did not have distinct and unique
determinants.

Work this year in my lab by David Paik (not published yet) has data
in the same ballpark as reported above.  We found a 17x increase in
the density of MNV by comparison to a mixed group of NL and AOD
controls.  We have already reported that the endothelial cell in
the MNV way be an important source of collagenase in the adventitia
(Newman et al).  Accordingly, the molecular drivers for MNV become
more interesting.  In our most recent unpublished work (with
Bhattacharia and colleagues) we have found expression of the
integrin, alpha V - beta 3, in endothelial cells of the MNV. 
Leaping way forward in thought, perhaps another pharmacological
intervention in AAA-susceptible individuals might be an inhibitor
of this integrin that has been implicated in neovascularization.


2.  Inhibition of aortic aneurysm development in blotchy mice by
beta adrenergic blockade independent of altered lysyl oxidase
activity.  MM Moursi, HG Beebe, LM Messina, TH Welling, and JC
Stanley.  J Vasc Surg  1995; 21: 792-800.

Abstract (condensed from authors): 

     Purpose:  To determine whether the effect of beta-blockers on
aneurysm development in susceptible mice is due to hemodynamic
effects or stimulation of the cross-linking enzyme lysyl oxidase
(LO).

     Methods:  Normal littermates, untreated blotchies, and treated
blotchies were the subjects of the experiments.

     Results:  All beta-blockers tested reduced aneurysmal
enlargement in the Blotchy mice (propranolol, atenolol, nadolol). 
However, they did not increase the measured activity of LO in the
test groups.

     Conclusion:  The authors conclude that the mechanism of
prevention of aneurysms in the beta-blocked mice is on the basis of
hemodynamic effects, rather than direct effects on connective
tissue.

Comment by mdt.   Well, maybe they're right.  But I think more
studies will be needed before the matter can be considered closed. 
I remember when Brophy and others were helping with similar
experiments back in the late 80's.  We kept a chart up on the
refrigerator door where the percent of insoluble collagen from skin
(which is distanced, you might say, from the hemodynamics of the
aorta) was posted each week, based on the last week's necropsies. 
I recollect these experiments as strongly supporting the notion
(first advanced by Boucek et al) that propranolol has a direct
effect on the toughness of connective tissue, even in skin.  

For the information of all inerested persons, the human
AAA/Propranolol Trial is seeking support, even as we speak, from
the NIH.  See other posts on my Home Page about the Prevention
Project under leadership of Mike Ricci at the University of
Vermont.