Acute Aortic Disease.. - Index of

136 Botta et al.
Table 2 Important Questions Regarding Matrix Metalloproteinases and
Aneurysm Disease
MMP’s are elevated in the wall of thoracic and abdominal aneurysms, but
Are these MMPs locally generated in the aortic wall, or systemically circulating,
due to general inflammation?
Are MMPs elevated only in the aneurysmal segment, or throughout the aorta?
Do circulating levels of MMPs correlate with tissue levels?
Can high circulating MMP levels serve as biomarkers of disease activity
or progression?
Can aneurysm expansion, dissection, or rupture be modified by pharmacologic
MMP manipulation?
Abbreviation: MMP, matrix metalloproteinase.
reflect a local pathologic process? Second, are the MMP levels elevated in the
aneurismal segment only or is the elevation measurable throughout the aorta?
Third, do circulating levels of MMPs reflect the tissue levels of MMPs? Fourth,
if circulating levels of MMPs reflect tissue levels, do higher MMP levels portend
more rapid expansion, and/or more frequent complications from TAAs? Finally,
can the expansion or complication rate of TAAs be modified by pharmacologic
MMP manipulation?
Systemic or local? To answer the first question, one must assess gene expression
at the tissue level of MMPs. If MMP levels were elevated without locally
increased gene expression, then the increased levels could simply be a reflection
of high systemic MMP levels. Conversely, if both the MMP levels and the gene
expression for these proteins are elevated, a localized process is more likely.
Indeed, we were able to demonstrate increased levels of MMP-1 and MMP-9,
at an RNA expression level (55). These findings are consonant with a cDNA based
micro-array study carried out by Taketani et al. with regard to MMP-9 gene
expression (61). They found elevated gene expression for MMP-1 and MMP-9 in
aneurismal aorta compared to adjacent, nonaneurysmal aorta. Thus, it certainly
appears that the MMPs are elevated at the aortic level, and this elevation is the
result of local production.
Localized or pan-aortic? To answer the second question as to whether this
MMP elevation is localized to the aneurismal segment or if a pan-aortic rise in
MMPs occurs, an elegant study was recently published by Sinha et al. which
measured MMP expression in descending thoracic aneurysms. They were able to
show increased MMP-9 expression in the more rapidly expanding anterior wall
of the aneurismal segment of the aorta compared to the more slowly growing posterior
wall at the same level, and compared to controls (57). Thus, the association
between local production of MMP-9 and aneurysm growth seems very clear.
Circulating levels reflective of tissue levels? The third question is whether
levels of MMPs are concordant between the aneurismal aortic tissue and the
circulation. If this correlation exists, it would allow us to gauge the pathologic
process involved with aneurysm expansion by means of a simple blood test.