Biology Reference
In-Depth Information
9.4.2 EFs Impact Cellular Behavior
Elastin fragments are capable of altering cell behavior by means other than simple
chemotaxis. Exposure of human skin fibroblasts to VGVAPG has been shown to
induce the expression of both MMP1 and -3 (Brassart et al.
2001
). EFs also
participate in angiogenesis, the process of new blood vessel formation, in the setting
of matrix injury. EFs can induce both cell migration and tubulogenesis of endothe-
lial cells (Robinet et al.
2005
). These effects are dependent upon the induction of
MMP2 and -14. Gene silencing of MMP14 abrogated endothelial cell motility and
morphogenesis, in this setting.
EFs likely exert their influence on cell behavior via interaction with 67-kDa
elastin-binding protein (EBP) (Mecham et al.
1989a
,
b
). Consistent with this
concept, the inhibition of EBP signaling eliminated the effects of VGVAPG
exposure with respect to MMP production in the above studies. The EBP is also
located on circulating lymphocytes. Interaction with EFs and lymphocyte-derived
EBP drives Th1 differentiation of CD4
+
cells in the setting of aortic aneurysm
(Debret et al.
2005
).
9.4.3 EFs as Biomarkers of Disease
Elastin degradation is relatively specific to disorders of the lung, skin, and blood
vessels. Investigators have attempted to measure EFs in the serum, urine, or BALF
as a measure of disease activity or severity, most commonly for emphysema and
aortic aneurysm (Luisetti et al.
2008
). Mature elastic fibers contain two unusual,
tetrafunctional, pyridinium ring-containing amino acids, desmosine (DES) and
isodesmosine (IDES) (see above). Assays have been developed that reliably detect
both DES and IDES in human serum and urine (Darnule et al.
1982
). Early
generation assays provided conflicting results with respect to DES as a biomarker
for emphysema. These assays were able to distinguish between smokers with
emphysema and healthy controls, but not between smokers with emphysema versus
smokers without the disease (Davies et al.
1983
). More recently, the introduction of
HPLC methodology has improved the resolution of these assays although they
remain tedious and provide a small signal.
Acute aortic dissection carries a high mortality and requires early surgical inter-
vention. Unfortunately, diagnosis of aortic dissection is extremely difficult and often
mistaken for acute coronary syndromes. Shinohara and colleagues recently reported
promising results, showing that EFs are present in
60% of patients with acute
aortic dissection but less than 5% of patient with acute myocardial infarction
(Shinohara et al.
2003
). Improvements in assay quality and especially rapidity will
be required if EF detection is to be used as a reliable diagnostic marker in patients
presenting with acute chest pain.
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