57
APRIL 24
TH
– 26
TH
, 2014 | OLOMOUC | THE CZECH REPUBLIC
ABS TRAC T BOOK
(růst) glyoblastomu je zatížen celou řadou molekulárních
a mutačních změn, které mohou v budoucnu změnit pohled
a terapeutické aspekty tohoto onemocnění.
17) Left and right atrial structural remodeling in
hearts of patients with sinus rhythm and atrial
fibrillation
Smorodinova N.
1
, Lantová L.
1
, Bláha M.
2
,
Melenovský V.
2
, Kautzner J.
2
, Kučera T.
1
1
Institute of Histology and Embryology, The First Faculty
of Medicine, Charles University in Prague, Prague
2
Institute for Clinical and Experimental Medicine-IKEM,
Department of Cardiology, Prague
Atrial fibrillation (AF) is one of the most common arrhy-
thmias in the clinical practice and it is associated with an
increase in mortality risk that is strongly related with old age.
Its pathogenesis is still not sufficiently explored. One of the
generally recognized factors contributing to the initiation and
maintenance of atrial fibrillation is structural remodeling of the
myocardium. Structural remodeling is reflected by changes
that affect both atrial cardiomyocytes as well as endomysium.
Aim:
In this work we focused on morphological charac-
terization of endomysium from both the left and the right
atrium in patients undergoing open heart surgery with atrial
fibrillation or in sinus rhythm. We also compared extracellular
matrix composition, VEGF immunoreactivity, and microvascular
density and microvessel pericyte coverage index between
patient groups and also based on localization.
Methods:
We studied functional morphology of atrial
biopsies performed at 46 patients (19 patients with AF, and
27 with sinus rhythm (SR)) undergoing bypass or mitral valve
surgery. The atrial samples were fixed with 4 % paraformal-
dehyde and embedded into paraffin. Sections from atrium
were histologically examined using routine hematoxylin-eosin
staining. Immunohistochemistry was used to visualize collagen
I, collagen III, elastin, desmin, smooth muscle actin and VEGF
in the atrial samples. To detect capillaries UEA-lectin was used.
Results:
We found variable amount of endomysial collagen
I and III in myocardial samples from both groups of patients,
which was similar when comparing SR and AF group and when
comparing left and right atrium as well. The amount of elastin
in the atria was similar in AF and SR groups but there was more
than twofold amount of elastin in the right atrium compared
to the left. Variable amount of VEGF was localized mainly in
the mesothelium, blood vessels and adipocytes, but also in
the cardiomyocytes. The expression of VEGF, microvascular
density and microvessel pericyte coverage index was similar
when AF and SR group was compared and also did not differ
between left and right atrium.
Conclusion:
Our results document that in patients under-
going open heart surgery variable level of ECM proteins can
be found but the amount of collagen I, colagen III and elastin
do not differ when the patient group is divided based on the
presence of atrial fibrillation or sinus rhythm. Elastin volume
fraction is higher in the right atrium compared to the left po-
ssibly reflecting different biomechanics or embryonic origin.
VEGF is present in myocardia of patients but its amount is not
dependent on the heart rhythm. Most of atrial capillaries are
associated with pericytes but similar to microvascular density
we did not observe changes during atrial fibrillation or when
left and right atrium was compared.
This work was supported by the Research Program of Charles
University – PRVOUK -P25/LF1/2.
18) MDM2 and MDMX in prostate cancer-
associated EMT: expression, localization and
effect on cell migration
Slabáková E.
1,2
, Kharaishvili G.
3
, Fedr R.
1
,
Smějová M.
5
, Remšík J.
1,4
, Pernicová Z.
1,2
,
Šimečková Š.
1,2
, Sedlmaierová E.
4
, Bednář P.
6
,
Bouchal J.
3
, Kozubík A.
1,4
, Souček K.
1,2
1
Academy of Science of the Czech Republic, Institute
of Biophysics, Department of Cytokinetics, Brno,
Czech Republic
2
International Clinical Research Center, St. Anne‘s
University Hospital Brno, Brno, Czech Republic
3
Laboratory of Molecular Pathology and Institute
of Molecular and Translational Medicine, Faculty
of Medicine and Dentistry, Palacky University, Olomouc,
Czech Republic
4
Department of Experimental Biology, Masaryk
University, Faculty of Science, Brno, Czech Republic
5
Department of Biology, Masaryk University, Faculty
of Medicine, Brno, Czech Republic
6
Department of Biochemistry, Masaryk University,
Faculty of Science, Brno, Czech Republic
Most cancer-related deaths are associated with advanced
disease and metastasis. Epithelial-mesenchymal transition
(EMT), in which epithelial cells lose their polarity and become
motile mesenchymal cells, is viewed as an essential step faci-
litating dissemination of tumor cells. While the EMT-inducing
transcription factors from the Snail, Twist and ZEB families are
important mediators of cancer progression and metastasis,
reports about expression of MDM2 and MDMX in cancer cells
and metastases are conflicting.
Apart from being a crucial regulator of the p53 tumor supp-
ressor, MDM2 cooperates with p53 in negative regulation of
an EMT-inducing transcription factor SNAI2/Slug, implying
that MDM2 can function as a regulator in the EMT process.
Analyzing paired benign and tumorigenic cell lines derived
from prostate and breast tissue, we observed that cancer
transformation is accompanied by EMT, downregulation of
MDM2 expression and upregulation of MDMX. Moreover, the
same trend was observed in a proportion of patient prostate
tissues obtained from primary tumors and their respective
metastases. The EMT status was evaluated based on the ex-
