Women’s Health and Cardiovascular Diseases
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Інститут молекулярної біології і генетики НАН України
2012
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irk-123456789-1568392019-06-20T01:26:19Z Women’s Health and Cardiovascular Diseases Abstracts of RECOOP HST Research Networks’ Invited Speakers 2012 Article Women’s Health and Cardiovascular Diseases // Вiopolymers and Cell. — 2012. — Т. 28, № 2, доп. — С. 24-35. — англ. 0233-7657 http://dspace.nbuv.gov.ua/handle/123456789/156839 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
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Abstracts of RECOOP HST Research Networks’ Invited Speakers Abstracts of RECOOP HST Research Networks’ Invited Speakers Women’s Health and Cardiovascular Diseases Вiopolymers and Cell |
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Women’s Health and Cardiovascular Diseases |
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Women’s Health and Cardiovascular Diseases |
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Women’s Health and Cardiovascular Diseases |
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Women’s Health and Cardiovascular Diseases |
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Women’s Health and Cardiovascular Diseases |
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women’s health and cardiovascular diseases |
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Інститут молекулярної біології і генетики НАН України |
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Abstracts of RECOOP HST Research Networks’ Invited Speakers |
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Women’s Health and Cardiovascular
Diseases // Вiopolymers and Cell. — 2012. — Т. 28, № 2, доп. — С. 24-35. — англ. |
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Вiopolymers and Cell |
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2025-07-14T09:09:52Z |
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2025-07-14T09:09:52Z |
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1837612865332183040 |
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24
Women’s Health and Cardiovascular
Diseases
25
The pathophysiological background of heart failure with preserved
ejection fraction (HFPEF)
Papp Z., Édes I., Kalász J., Czuriga D., Balogh Á., Borbély A.
UDMHSC, Institute of Cardiology, Division of Clinical Physiology, Center of Excellence,
Móricz Zs. krt. 22. H-4032, Debrecen, Hungary
pappz@dote.hu
Aim: We aimed to characterize the myofibrillar components of diastolic heart failure
(heart failure with preserved ejection fraction (HFPEF)).
Methods: Biophysical and biochemical characteristics of permeabilized cardiomyocytes
isolated from left ventricular biopsies of patients with or without HFPEF, and/or with
aortic stenosis (AS), or diabetes mellitus (DM) were determined under in vitro
conditions.
Results: Passive force (Fpassive) of cardiomyocytes isolated from HFPEF patients was
significantly higher than in controls. Moreover, Fpassive correlated with left ventricular
end-diastolic pressure (LVEDP) and left ventricular (LV) end-diastolic wall stress. High
Fpassive of cardiomyocytes from HFPEF patients was reversible as it was normalized
following the in vitro administration of protein kinase A (PKA) or protein kinase G
(PKG) or antioxidants (e.g. dithiothreitol). The three-fold rise in Fpassive of HF
cardiomyocytes compared to AS cardiomyocytes was partially attributed to a shift in titin
isoform phosphorylation with relative hypophosphorylation of the stiff N2B titin isoform
when compared to that of the more compliant N2BA isoform. Fpassive was augmented in
patients with AS and DM. An additional component of increased cardiomyocyte passive
stiffness was associated with myofilament protein oxidation.
Conclusions: Changes in the levels of expression, phosphorylation and oxidation of
myofibrillar proteins of LV cardiomyocytes may contribute to the development of
HFPEF.
Keywords: heart failure, diastolic dysfunction, cardiomyocyte, passive force, human
myocardial biopsy
26
Gene for connexin 37 and cardiovascular risk
Piťha J.
Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine,
Vídeňská 1958/9, 140 21, Prague, Czech Republic
japi@medicon.cz; japi@ikem.cz
Aim: The aim of this presentation is to discuss gene-environment interaction in the
development of cardiovascular disease. This will be demonstrated on the example of the
gene for connexin 37. Previously, we observed that the association between this gene and
risk for ischemic heart disease (IHD) is modified by female gender and smoking.
Recently, we further expanded the data by measuring this gene polymorphism in patients
with IHD from Hungary and Croatia.
Methods: Study population comprised 704 women and 1, 884 men with IHD. As a
control group we used population of 1,368 women and 1,191 women from the population
based (post-MONICA) study. We compared the prevalence of connexin 37 gene variants
between patients and controls after stratifying them by gender and smoking status.
Differences were evaluated by chi-square test (STATA program).
Results: The frequency of genotypes in the whole group significantly differed between
women smokers and non-smokers with IHD. There was significantly lower frequency of
T allele in women non-smokers than in women smokers, with IHD (nonsmokers: TT, CT
and CC: 9.5, 37.7 and 52.8 %, smokers: 12.4, 44.5 and 43.1 %, p = 0.038). Significant
differences were also found between women with IHD and control population with
regard to smoking status. No such differences were found in male population. Similar
results were observed in the population from Romania, with borderline significance (p =
0.09). Data from Hungary and Croatia when stratified by gender and smoking status did
not reach statistical significance because of smaller sample size.
Conclusion: Our results indicate that the T allele could be protective against
manifestation of ischemic heart disease in female non-smokers while male gender and
history of smoking abolishes this positive effect. In general, impact of particular gene
variant could be extremely dependent on risk profile of the population under study.
Key Words: connexin 37 gene – ischemic heart disease- gender – smoking
27
Advanced glycation end products, insulin sensitivity and central
obesity: gender-specific associations
1Šebeková K., 2Krivošíková Z., 2Gajdoš M.
1Faculty of Medicine, Comenius University,
Sasinkova 4, 811 08 Bratislava, Slovakia
2Faculty of Medicine, Slovak Medical University,
Limbová 14, 83303 Bratislava, Slovakia
kata.sebekova@gmail.com
Aim: We studied the gender-specific differences in advanced glycation end-products
(AGEs) and advanced oxidation protein products (AOPPs) in young-to-early-middle-
aged general population.
Methods: In 437 (183M/254F) apparently healthy volunteers aged 33±11 years plasma
levels of Nε-(carboxymethyl)lysine (CML, chemically defined AGE product), AGE-
specific fluorescence, levels of soluble receptor for AGEs (sRAGE) and advanced
oxidation protein products were determined. Waist circumference was recorded and
insulin sensitivity was determined (Quantitative insulin-sensitivity check index -
QUICKI). Student’s T-test was used to compare 2 groups, and General linear model to
assess the impact of gender, waist circumference and insulin sensitivity on above
mentioned biomarker’s levels.
Results: Males and females did not differ significantly by age and QUICKI. Males
presented higher waist circumference (M: 93±11 cm, F: 78±11 cm, p<0.001), lower CML
(M: 1.2±0.2 ug/ml, F: 1.3±0.3 cm, p<0.001), and sRAGE (M: 1.2±0.4 ng/ml, F: 1.3±0.4
ng/ml, p<0.05) levels, but higher AOPPs (M: 79±47 umol/l, F: 70±40 umol/l, p<0.02).
No significant difference in AGE-specific fluorescence was revealed. General linear
model revealed that waist circumference imposed the main significant impact on CML,
fluorescent AGEs and sRAGE levels. It failed to reveal significant gender-specific
impact, effect of waist circumference or QUICKI on AOPP levels
Conclusions: Mild but significant differences in plasma CML and sRAGE between
young-to middle-aged apparently healthy males and females are mainly on the account of
waist circumference.
Keywords: central obesity, insulin sensitivity, gender, advanced glycation end products,
sRAGE, advanced oxidation protein products
Aknowledgement: Study was supported by the grant from the Ministry of Health of the
Slovak Republic, No.: 2005/27-SZU-05.
28
Cellular mechanisms for diastolic dysfunction in the human heart
Borbély A., Czuriga D., Édes I., Papp Z.
University of Debrecen, Medical and Health Science Center, Institute of Cardiology,
H-4032 Debrecen, Móricz Zsigmond krt. 22, Hungary
borattila@freemail.hu
Left ventricular diastolic dysfunction (DD) occurs in various cardiovascular diseases. DD
develops during normal cardiac aging and manifests not only in heart failure with
preserved and reduced ejection fraction (HFPEF and HFREF, respectively), but also in
diabetic cardiomyopathy, aortic valve stenosis, hypertrophic cardiomyopathy (HCM) and
Fabry disease (FD). Mechanisms leading to DD are divergent, and involve
cardiomyocyte dysfunction, transcriptional and post-translational myofilamentary protein
alterations, as well as abnormalities of the extracellular matrix. Moreover, the relative
contribution of the distinct territories widely differs among these diseases.
Increased collagen deposition along with collagen cross-linking by advanced glycation
end-products (AGEs) is proposed as the main determinant in the senescent heart.
Increased production of reactive oxygen species and involvement of the renin-
angiotensin system have been implicated in the background of fibrosis. In HFPEF high
cardiomyocyte resting tension was shown to contribute to the myocardial stiffening.
Elevated cardiomyocyte resting tension was also implicated in diabetic patients with
HFNEF, whereas in diabetic patients with HFREF AGEs deposition and fibrosis were
identified as major contributors to increased LV stiffness. In contrast to HFNEF, patients
with aortic valve stenosis develop not only diastolic, but also systolic dysfunction, which
is attributed to a complex inflammatory process involving similar mechanisms as those
leading to atherosclerosis. Genetically determined diseases (HCM and FD) also exhibit
diastolic dysfunction. While in HCM mutation of a sarcomeric protein leads to
development of myocardial remodeling, FD is associated with an enzyme deficiency,
which induces the progressive glycosphingolipid deposition in cardiomyocytes and
consequent contractile dysfunction.
The divergent set of mechanisms underlying impaired diastolic function requires not only
complex experimental and clinical investigations, but also individually designed
therapeutic approaches, which aim to improve the function of the pathologically
remodeled heart.
Keywords: cardiomyocytes, contractile dysfunction, diabetes mellitus, diastole, fibrosis,
human heart.
29
Vitamin D status in Slovak population.
Krivošíková Z., Gajdoš M.
Slovak Medical University, Faculty of Medicine,
Limbová 12, 833 03 Bratislava, Slovakia
riaditel.vvz@szu.sk; martin.gajdos@szu.sk
Aim: The key role of vitamin D (VD) in the control of bone metabolism, Ca and P
homeostasis is well-known. VD acts through vitamin D receptor and directly or indirectly
affects the transcription of more than 200 target genes. Except skeletal effects, there are
also a wide variety of non-skeletal effects of VD on the regulation of the cell
differentiation and proliferation, hormones secretion and on the modulation of immune
system. There is a lack of data on VD deficit in Slovakia. Thus, the aim of our study was
to determine VD status in healthy adults in Slovakia.
Methods: The study sample comprised 1213 apparently healthy subjects (851F/ 362M)
drawn from existing prospective cohorts of adults living in Bratislava and west Slovakia.
The study was carried out during winter and spring. No supplementation of VD was
allowed. Body mass index (BMI) was calculated and serum concentrations of 25-
hydroxyvitamin D (25(OH) D) and intact parathormone (PTH) were analysed.
Results: The genders were similar in age range (F: 15-80; M: 15-83), but men had
significantly higher BMI (p<0.0001) and 25(OH) D (p<0.0001) and lower PTH
(p<0.041). Strong relationship between 25(OH)D and BMI (p<0.0004) was found in all
group and in both geneders separately. A similar pattern emerged for the association
between 25(OH)D and age (p<0.0002). VD insufficiency (20-30 ng/ml) was found in
26% of men and in 30% of women (p<0.001) and VD deficit (<20 ng/ml) was found in
29% of men and in 36% of women (p<0.001).
Conclusion: VD deficiency and insufficiency are common in Slovak healthy adults. Low
VD levels correlates with age, BMI and sex. Due to the possible links between low VD
status and disease risk we recommend to improve vitamin D intake through supplements.
Supported by: Research and development program financed from the European Regional
Development Fund, project ITMS No.24240120033.
Key words: vitamin D status, population
30
Simultaneous quantification of soluble fibrin, DD and Fg in clinics
Lugovskoi E. V., Kolesnikova I. N., Komisarenko S. V.
AV Palladin Institute of Biochemistry, NAS of Ukraine
9, Leontovicha Str. Kiev, Ukraine, 01601
lougovskoy@yahoo.com
Aim: To show the diagnostic importance of simultaneous quantification of soluble fibrin
(Sf), D-dimer (DD) and fibrinogen (Fg) at various diseases.
Methods: Quantification of Sf, DD and Fg was performed by ELISA using three test-
systems designed in our department.
Results: Quantification of Sf and DD in donor blood plasma showed that Sf
concentration is on average 3-3.5 g/ml and DD concentration – 120 ng/ml. Such
measurements give integral information about the state of coagulation system and
fibrinolysis at TELA, DVT, DIC syndrome, caesarean operation, arteriovenous form of
angiodisplasy, and abdominal aortic aneurysm. Simultaneous measurements of Sf, DD
and Fg are useful to diagnose and monitor antithrombotic and thrombolytic therapy
including post-operation period. It has been shown the increased concentrations of these
molecular markers positively correlate with the seriousness of blood vessel complications
in patients, suffering from diabetes mellitus.
Conclusions: Simultaneous quantification of Sf, DD and Fg gives very useful diagnostic
information about the state of haemostasis system.
Fig. Soluble fibrin and D-dimer contents in blood plasma of health individuals (N) and
patients suffering from diabetes mellitus with initial (1), medium (2) and severe (3) blood
vessel complications.
Keywords: soluble fibrin; DD; fibrinogen; simultaneous quantification in clinics
Soluble fibrin
0.0
2.5
5.0
7.5
10.0
N 1 2 3
[S
F
],
g
/m
l
D-dimer
0
25
50
75
100
125
150
175
N 1 2 3
[D
D
],
n
g
/
m
l
31
Cellular cardiomyoplasty: new possibilities
Lukash L.L.
Institute of Molecular Biology and Genetics of NAS of Ukraine
150, Zabolotnogo Str., Kiev, Ukraine, 03680
lukash@imbg.org.ua; imbig@serge.relc.com
Aim: Nowadays conception of cellular cardiomyoplasty consist in preventing the
progression and consequence of cardiac disease (CD), and also enhancing regeneration of
damaged tissues. Cell-based myocardial regeneration is currently being explored for a
wide range of CD, including acute and chronic ischemic myocardial damage and
cardiomyopathy. The goal of cell therapy for heart failure is improving cardiac function,
accordingly with inhibition of remodeling process. Ideally, transplanted stem cells (SCs)
would replace and mimic the lost cardiomyocytes morphologically and functionally
showing the ability to contract and to establish electrical connectivity with the native
cells.
Methods: Different SC types have been tested and the methods of their introduction and
delivery to damaged myocardium have been developed by using experimental models.
Results: At least two types of bone marrow-derived SCs, skeletal myoblasts, cardiac
stem and progenitor cells, embryonic SCs, endothelial progenitor and precursor cells
have been investigated in experimental models, and they revealed different potential for
differentiation to cardiomyocytes and stimulation of myocardial regeneration. Two
fundamental mechanisms by which SCs may repair damaged myocardium have been
established: 1) direct or indirect improvement of neovascularization; 2) differentiation
into cardiomyocytes and formation of heart tissue. Functional improvement may also be
mediated through paracrine secretion of growth factors and cytokines which indirectly
promote survival of cardiomyocytes by inhibition of apoptosis, and may also lead to
mobilization of endogenous progenitor cells. Address delivery of SCs to damaged
myocardium zones is being developed by using nanoparticles in experimental models.
During last years a few clinical protocols have been approbated in clinics of USA,
Europe and Russia.
Conclusions: According the results of selected clinical trials the methods of cellular
cardiomyoplasty are safe for health of patients and their application in the scheme of
treatment lead to improvement of cardiac function. But there is a big difference in
individual response on the introduction of exogenous cells or cellular products.
Keywords: cell cardiomyoplasty, stem cells, myocardial regeneration
32
Transcardiac gradients of IL6, TNFa and adiponectin in CAD
patients
1Sram M., 2Vrselja Z., 2,3Leksan I., 2Radic R.
1Clinical Hospital Center, Clinic for Internal Medicine, Dept. of Cardiology,
J Huttlera 4, 31000 Osijek, Croatia
2University J J Strossmeyer, School of Medicine, Dept of Anatomy and neuroscience,
J Huttlera 4, 31000 Osijek, Croatia
3 Clinical Hospital Center, Clinic for Surgery, Dept. of Cardiac Surgery,
J Huttlera 4, 31000 Osijek, Croatia
rradic@mefos.hr
Aim: Adiponectin (ADIPOQ), protein produced by adipose cells, has antiatherogenic
effect while interleukin 6 (IL6) and tumor necrosis factor (TNFa) have proatherogenic
effect. Aim of this study was to determine concentrations of ADIPOQ, IL6 and TNFa in
aortic root (AR) and coronary sinus (CS) along with transcardiac gradients in CAD
patients.
Methods: Of 36 patients who underwent coronarography 16 of them had CAD. Blood
samples were taken from AR and CS. Concentrations of IL6, TNFa and ADIPOQ were
obtained by commercially available kits.
Results: IL6 showed a decrease in concentration from AR to CS, CAD patients had
significantly higher concentrations (p=0.012) (5.81 Me=5.10; 4.35 Me=4.50 pg/ml) in
CS. TNFa did not show significant difference throughout heart and in between groups.
CAD patients had significantly lower (p<0.001) concentrations of ADIPOQ in AR (2.67
± 1.27; 5.68± 3.10 µg/ml) and significantly lower (p=0.002) concentrations in CS (3.89 ±
2.23; 6.86 ± 3.57 µg/ml). Transcardiac gradient, concentration ratio of coronary sinus to
aortic root, with average value for IL6 less than 1, did not show significant difference
between groups, same as TNFa, where ratio was barely above 1.There was no significant
difference between groups. Transcardiac gradient for ADIPOQ was significantly higher
(p=0.018) in CAD group (1.47 ± 0.31; 1.23 ± 0.25).
Conclusions: CAD patients have decreased levels of adiponectin, higher transcaridac
gradient and increased levels of IL6 in CS.
Keywords: adiponectin, CAD, adipose tissue
33
Anti-mullerian hormone and cardiovascular protection
Tatarchuk T., Burlaka O., Rudenko N., Shapovalova V., Maksimenko V.
M. Amosov National Institute of Cardiovascular Surgery, Institute of Pediatrics, Obstetrics and
Gynecology, National Academy of Medical Science of Ukraine.
doctorsteb@rambler.ru
Aim: To study dynamics of anti-mullerian hormone (AMH) for perimenopausal women
for timely correction of menopausal disorders and prevention of cardiovascular accidents.
Methods: Levels of AMH, low-density lipoprotein-cholesterol (LDL-C), numbers of
antral follicles (AF) by ultrasound scan, were studied on 69 women (age 46,69±3,21
y.o.), who have initial involutive changes. 39 women (group I) have cardiovascular
diseases (CVD) history (arterial blood pressure > 135/85 mmHg and/or heart attack
episodes), 30 women (group II) don’t have CVD history.
Results: Group I: noted positive correlation between AMH level (0,54±0,38 ng/mL) and
numbers of AF (2,28±1,32) (r= +0,85); also noted negative correlation between AMH
and LDL-C (132,97±8,86 mg/dL) (r= -0,54). Group II: AMH level was 2,58±0,32
ng/mL, LDL-C level was 105,04±12,3 mg/dL (r AMH-LDL-C= -0,46); numbers of AF
were 4,92±1,35 (r AMH-AF = +0,76). In 27 women from I group after 3 month of
Replacement Hormone Therapy (RHT) LDL-C decreasing from 134,82±9,94mg/dL to
119,27±4,45mg/dL, (p<0,05). These changes were accompanied by reduced numbers of
CDV events and reduction of early climacteric symptoms. In 12 women from I group,
who didn’t use RHT, trends to increasing of LDL-C were detected (from
129,±5,17mg/dL to 136,41±2,32), numbers CDV events did not change, climacteric
autonomic disorders and anxious or depressive episodes were continued.
Conclusions: AMH control for perimenopausal women with CVD history must be done
every 3 month for timely correction of menopausal disorders and prevention of
cardiovascular accidents. Reduction of AMH for perimenopausal women more than
factor of 10 within a short time is the evidence of premature aging of the ovarian and of
lowering of hormonal protection of vessels. Appointment of RHT for hormone deficiency
contributes into the normalization of lipid profile, CVD prevention and the improvement
of quality of life.
Key words: Anti-Mullerian Hormone, cardiovascular risks, Replacement Hormone
Therapy.
34
Should C-reactive protein be linked with some noninvasive
parameters for improving the prognosis in acute coronary
syndrome patients
Lukin A.
Department of Cardiology, Clinical Hospital Center Split, Split, Croatia
ajvor.lukin1@st.t‐com.hr
Aim: C-reactive protein (CRP), when associated with noninvasive parameters, improves
prediction of outcomes in patients with acute coronary syndrome (ACS). The aim of this
study was to improve the prognostic and predictive value of C-reactive protein (CRP) in
acute coronary syndrome (ACS) settings by combining it with a number of other
noninvasive parameters obtained at the time of presentation to the hospital, creating
simple procedure affordable to majority of doctors.
Methods And Results: When CRP is linked to certain noninvasive parameters, such as
risk factors number, leukocytes, hemoglobin, total cholesterol, low-density lipoprotein,
total cholesterol and high-density cholesterol ratio, microalbuminuria, brain natriuretic
peptide or its precursor, fibrinogen, antithrombin III, troponin, duration of QRS complex,
ventricular ectopic activity by Lown’ classification, NYHA functional class, standard
deviation of all normal nonectopic RR intervals, silent and symptomatic myocardial
ischemia observed by ambulatory electrocardio-graphic monitoring and pulse recovery
after treadmill exercise testing, accurately prediction of the medium-term outcome in
patients with ACS can be achieved. To obtain such prognosis, the author has created
original score procedure.
In order to create conditions for comparing different indicators transformation of all these
parameters was made to form a unique scoring system. Values of parameters were
classified into three basic groups: normal, less adverse and more adverse. Nominal values
of parameters were associated with the empirically-driven numerical values. An award
system of parameters was created, and dependent relationship as well, which made
possible calculation of the medium-term prognosis in ACS patients.
Sbv = (CRPCRPbv) +(NeP NePbv)
35
SUM OF CRP AND 18 PARAMETERS CONVERTED VALUES
Pyramid of outcomes is also an empirical product which, based on the summary score of
CRP and the selected parameters, allows easy and reliable classification of patients with
ACS the risk groups, and consequently, the individualization of further therapeutic
procedures or treatment on each patient.
Based on the hypothesis testing was performed on 247 patients lasting more than two
years.
Test results have confirmed the validity of the hypotheses.
Conclusion: Study has confirmed that the prognostic value of CRP in ACS patients can
be improved, by linking CRP with some noninvasive parameters. New system of values
was created; the prognostic relations and the Pyramid of the outcomes were formed.
The intension of the author is to make software program in order to simplify procedure.
Key Words: C-reactive protein, Acute Coronary Syndrome, Unstable Angina, NSTEMI,
STEMI
STABLE CLINICAL
COURSE
≤ 15
16–25
26–31
≥ 32
GENERALLY
STABLE CLINICAL
COURS
CERTAINLY UNSTABLE
CLINICAL COURSE
LIFE THREATENED
CONDITION
|