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| 2 | 2011
Klinisk Biokemi i Norden
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Fortsat fra side 39)
information (30). A problem which has limited the
potential of genomic and transcriptional markers is
the rapid degradation of DNA and mRNA in plasma
and serum. In contrast, miRNA has been found to be
remarkably stable in plasma and serum, including in
samples that have been stored in room temperature for
hours (31). Of note, the stability of endogenous miRs is
not related to the size or composition of the RNA strand
as synthetic (exogenous) miRs are degraded within
minutes in serum and plasma samples (31). The model
for the stability of endogenous miRNA in peripheral
blood is still work in progress, but the inclusion of the
miRNA strand in exosomes (19), which are 40-100 nm
diameter lipid complex vesicles that are released from
the cell, together with miRNA-protein-interaction (32)
seem to be of paramount importance. Adding excite-
ment to this discovery, recent data from animal models
have suggested that both the release from the donor
cell and the endocytosis in the recipient cell are highly
specific, promoting a model of a new endocrine system
that allow cell-to-cell transport of miRs (19,33). This
model is supported by data showing limited correlation
between the miRs expressed in a patient’ blood cells and
the miR profile in the serum of the same patient (20).
Moreover, in an experimental model of prostate cancer,
miRs associated with the malignancy were increased in
the circulation after tumor growth (31), which points to
a disease-associated release of miRs to the circulation.
Adopting this to cardiac disease, this would suggest that
myocardial cells can release miRNA to the circulation,
and that this release would at least partly be regulated
by exocytosis. Based on this new knowledge, and the
earlier studies showing disease-associated alterations
in myocardial miR profile, miRNA biomarkers could
prove to be important. The first report to capitalize on
this was a Japanese group that identified miR-208 as a
cardiac-specific miR by microarray analysis, and then
demonstrated a time-dependent rise-and-fall pattern
of miR-208 in the circulation after myocardial injury
Foto: Henrik Alfthan
