Aneurysm Papers of the Month - September 1995

1. Tilson MD.  Similarities of an autoantigen in
aneurysmal disease of the human aorta to a 36-kDa
microfibril-associated bovine aortic glycoprotein. 
Biochem Biophys Research Comm  1995; 213: 40-43.

Abstract 

     Summary:  IgG from human aneurysmal aorta was used
to partially purify an aortic protein with an apparent MW
~80 kDa.  Amino acid sequencing of a tryptic digest
revealed two sequences with homology to mouse tenascin-X. 
The autoimmune IgG was then shown to react with purified
human tenascin, and a rabbit polyclonal anti-human
tenascin antibody was found to react with the purified
autoantigen.  We hypothesize that the autoantigen of
abdominal aortic aneurysm disease may be homologous to a
calcium-binding member of the tenascin superfamily that
has been identified by others in pig and cow.

     Last paragraph of discussion:  The putative
autoantigen in AAA disease may be a cleavage product of
one of the large members of the tenascin superfamily, but
an especially interesting possibility is that it might be
a human homologue to an aorta-specific microfibril-
associated glycoprotein (MAGP-36) described by Kobayashi
in pig and cow.  MAGP-36 has both calcium-binding and
tenascin-like domains.  It has a MW of 36 kDa, but it
occurs naturally as a dimer.  Its tissue localization is
limited to the aortic adventitia in the pig, and fine
structural immunomicroscopy further specified its
localization to elastin-associated microfibrils
(Kobayashi).  It seems reasonable to postulate the
existence of a human homologue and to speculate that this
protein may play an important role in aneurysmal disease
of the abdominal aorta.

Comment by mdt:  The hypothesis is alive and well.  We
have found that IgG from AAA patients is
immunohistochemically reactive with the adventitial
elastin-associated microfibril (Archives of Surgery, in
press).  Also, we are finding that the preparative yields
are greatly increased by extracting tissue under strong
reducing conditions, so we hope to have additional amino
acid sequence soon.  Ultimately, we aim to clone the cDNA
from an expression library.

2. Satta et al.  Increased turnover of collagen in
abdominal aortic aneurysms, demonstrated by measuring the
concentration of the aminoterminal propeptide of type III
procollagen in peripheral and aortic blood samples.  

Abstract (condensed from authors): 

     Background: The major collagens in aortic wall are
types I and III.  The authors investigated whether the
peptides of I and III were detectable in serum as a
reflection of increased  collagen turnover.

     Methods:  Radioimmunoassay of the aminoterminal III
propeptide and the carboxyterminal I, in 87 AAA patients
and 90 control patients with atherosclerotic occlusive
disease.

     Results:  There was approximately a 25% increase in
serum III propeptide in AAA versus controls (p < .0001),
and serum level was positively correlated with aneurysm
diameter (p = .04) and max thickness of intraluminal
thrombus (p = .003).

     Conclusion: Collagen III turnover is increased in
AAA.

Comment by mdt:  Busuttil and coworkers first proposed
that collagen turnover might be increased in 1980, and it
took me eight years to see the light (Tilson & Roberts,
Molecular heterogeneity in the aneurysm phenotype, Arch
Surg 1988; 123: 1202-6).  By 1990 I had become convinced
that instability of the collagen was a necessary feature
of AAA (Tilson et al, Tensile strength and collagen in
AAA disease, in Greenhalgh, Mannick, and Powell: The
cause and management of aneurysms, WB Saunders, London,
1990, pages 97-104).  The present paper is an important
contribution to the field and offers another possibility
for the development of a useful blood test.

3.  Cenacchi G, et al.  The morphology of elastin in non-
specific and inflammatory AAA: A comparative transmission
(TEM), scanning (SEM) and immunoelectronmicrosopy study. 
J Submicrosc Cytol Pathol  1995; 27: 75-81.

Abstract (condensed from authors): 

     The techniques mentioned in the title were used to
evaluate modifications of elastin in non-specific AAA's
(NSAAA's) and inflammatory AAA's (IAAA's).  Both lesions
were characterized by extensive matrix remodelling, with
the changes being more extensive in IAAA.  Even in the
NSAAA's the morphology was so modified that
identification by TEM had to rely on immunocytochemical
methods and SEM.  

Comment by mdt.  This brief abstract does not do this
paper justice, and the reader is referred to the original
for beautiful illustrations.  I shrink from making
critical comments (because to the best of my knowledge it
is only the second high-quality fine structural study in
the world literature), but the authors do misquote me:
"Histological properties of the elastin residue itself
were reported to be normal (Tilson and Roberts, 1988)". 
Actually, Roberts and I wrote about molecular diversity
in the aneurysm phenotype.  I published a paper about the
same time (Tilson, Arch Surg 1988; 123: 503-5) pointing
out several abnormal features of aortic elastin in AAA. 
Derangements of elastin are easily demonstrated.  The
most interesting question is whether or not the
destruction of elastin, with the liberation of elastin
degradation products, is necessary for eventual collagen
failure (with gross dilation of the AAA).   See
discussion of paper #2 above for related information.