Pobierz PDF

original papers
Adv Clin Exp Med 2013, 22, 6, 801–807
ISSN 1899–5276
© Copyright by Wroclaw Medical University
Małgorzata Michalska1, B–F, Iza Iwan-Ziętek1, 3, C, D, Włodzimierz Gniłka2, B, D,
Stanisław Dąbrowiecki2, C, E, Barbara Góralczyk1, B–D, Krzysztof Góralczyk1, B, C, E,
Ewelina Drela1, F, Danuta Rość1, A, C, E, F
PAI-1 and a2-AP in Patients with Morbid Obesity
PAI-1 and a2-AP u chorych z otyłością olbrzymią
Department of Pathophysiology, the Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus
University in Toruń, Poland
2
Department of General, Vascular and Endocrine Surgery, the Ludwik Rydygier Collegium Medicum
in Bydgoszcz, Nicolaus Copernicus University in Toruń, Poland
3
Aesthetic Dermatology Laboratory of the Department of Dermatology PUM in Szczecin, Poland
1
A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation;
D – writing the article; E – critical revision of the article; F – final approval of article; G – other
Streszczenie
Background. Obesity is a multifactorial, progressing and life-long illness that consists in an exaggerated collection of fatty tissue. In 1997 WHO acknowledged that overweight and obesity had the character of an epidemic in
developed countries. Studies show that in Poland morbid obesity was diagnosed in 2.2% of women and in 0.6% of
men. Thromboembolic incidents occur very often in people with obesity, especially with morbid obesity. In hypercoagulability, fibrinolysis process decides about the scale of clinical symptoms of disorders of the hemostasis.
Objectives. The aim of this study was to assess the chosen parameters of the fibrinolysis process in patients with
BMI crossing 40, classified for surgical treatment of obesity.
Material and Methods. The study was conducted in 50 patients with BMI > 40, including 30 women and 20 men.
The mean age of the patients was 38.5 years. The control group was made up of 20 healthy volunteers, with a mean
age of 38 years. In the blood of both groups the following examinations were performed: concentration of tissue plasminogen activator antigen (t-PA:Ag), antigen of the plasminogen activator inhibitor type-1 (PAI-1:Ag),
D-dimers, fibrinogen and plasminogen, activity of the a2-antiplasmin (a2-AP)
Results. The conducted study showed that in patients with morbid obesity there was a higher concentration of
tPA:Ag, PAI-1:Ag, D-dimers and a higher activity of a2-AP.
Conclusions. The conducted study demonstrates that the activation of the fibrinolysis process appeared after the
coagulation process, indicated by an increase in the t-PA:Ag concentration and D-dimers concentration in patients
with morbid obesity. The essential growth of PAI-1:Ag level and a2-AP level shows strong inhibition of fibrinolysis
in patients (Adv Clin Exp Med 2013, 22, 6, 801–807).
Key words: morbid obesity, fibrinolysis, PAI-1:Ag, a2-AP.
Streszczenie
Wprowadzenie. Otyłość jest wieloczynnikową, postępującą i trwającą przez całe życie chorobą polegającą na nadmiernym gromadzeniu tkanki tłuszczowej. WHO w 1997 r. uznała, że nadwaga i otyłość w krajach rozwiniętych
mają charakter epidemii. Badania wykazują, że w Polsce otyłość olbrzymią rozpoznano u 2,2% kobiet i 0,6 % mężczyzn. U osób z otyłością, szczególnie olbrzymią, dochodzi bardzo często do powikłań zatorowo-zakrzepowych.
W sytuacji nadkrzepliwości krwi o skali objawów klinicznych zaburzeń hemostazy decyduje układ fibrynolizy.
Cel pracy. Ocena wybranych parametrów układu fibrynolizy u chorych z BMI przekraczającym 40, zakwalifikowanych do operacji chirurgicznego leczenia otyłości.
Materiał i metody. Badanie przeprowadzono w grupie 50 chorych z BMI > 40, w tym 30 kobiet i 20 mężczyzn,
w wieku 21–60 lat (średnio 38,54). Grupę kontrolną stanowiło 20 zdrowych ochotników w wieku 22–52 (średnio 38,0) lat. W obu grupach wykonano następujące badania krwi: stężenie antygenu tkankowego aktywatora
802
M. Michalska et al.
plazminogenu (tPA:Ag), antygenu inhibitora aktywatora plazminogenu typu 1 (PAI-1:Ag), D-dimerów, fibrynogenu i plazminogenu, oraz aktywność a2-antyplazminy (a2-AP).
Wyniki. Przeprowadzone badania wykazały, że w grupie chorych z otyłością olbrzymią występuje zwiększone stężenie tPA:Ag, PAI-1:Ag, D-dimerów oraz a2-AP.
Wnioski. Przeprowadzone badania wykazały, że u chorych występuje aktywacja fibrynolizy wtórna do procesu
krzepnięcia, wyrażona wzrostem stężenia t-PA:Ag i D-dimerów. Bardzo znaczne zwiększenie stężenia PAI-1:Ag
i a2AP we krwi chorych z otyłością olbrzymią wskazuje na silne hamowanie procesu fibrynolizy (Adv Clin Exp
Med 2013, 22, 6, 801–807).
Słowa kluczowe: otyłość olbrzymia, fibrynoliza, PAI-1:Ag, a2-AP.
Obesity is multifactorial, progressing and lifelong disease that consists in an exaggerated collection of fatty tissue. This disease constitutes a grave
medical problem, and the number of obese patients is growing. In 1997 WHO acknowledged
that obesity had the character of an epidemic in
developed countries [1]. It is estimated that in the
whole world, 60% of people have excess weight and
obesity in a different degree. In the USA the percentage of obese people is particularly large. 33.6%
of Americans were stated to be overweight, in 23.9
% obesity was demonstrated, and in 3% morbid
obesity [2].
In Poland, on the basis of WOBASZ research,
40.4% of men and 27.9% of women were found to
be overweight, and 20.2% of women and 20.6% of
men were obese. Studies show that in Poland morbid obesity was diagnosed at 2.2% of women and
0.6% of men [3].
The etiology of obesity is not fully understood;
it is considered that obesity development is related to:
–  genetic factors,
–  age, obesity may occur at any age but its incidence increases with age,
–  sex, women usually have a higher BMI than
men,
–  physiological factors such as pregnancy, puberty, menopause, andropause,
–  economic and social conditions; most obese
groups are found with low economic status,
–  psychological factors such as depression,
–  eating disorders, both diet and consumed
high-calorie meals may lead to the development of
obesity,
–  some medication, such as antidepressants or
anticonvulsants [4].
Clinical and laboratory studies indicate that
adipose tissue in obese individuals located in the
abdominal region is the endocrine organ and secretes a hormone factors. These factors are adipocytokines which include: lectin, adiponectin,
resistin, tumor necrosis factor a (TNF-a) or plasminogen activator inhibitor-1 (PAI-) [5].
Obesity involves many metabolic disorders. They include carbohydrates disorders such
as impairment glucose tolerance and insulin
resistance [6]. An increased concentration of trigly­
cerides, an increased concentration of LDL cholesterol and a lowered concentration of HDL cho­
lesterol in serum are observed in obese patients.
The impairment of the coagulation process is noted and appears as hypercoagulability [5, 6].
It is known that obesity constitutes a danger to
health and lives. An increasing mortality is its disadvantageous result; in addition, the risk of death
increases along with an increasing BMI [7]. Mortality associated with obesity results from a much
more frequent appearance of cardiovascular diseases: arterial hypertension, atherosclerosis, ischaemic heart disease and varicose veins of lower limbs.
Thromboembolic complications, which are the
direct cause of death in vascular diseases, affect very
often persons with obesity, especially with morbid
obesity. Disturbances in hemostasis, which include
the exaggerated activation of the coagulation pro­
cess and the inhibition of the fibrinolysis, have a deciding impact on the development of these changes. The changes in the coagulation process in obese
people include: increased concentration and activity of the coagulation factors, increased aggregation
of the platelet, hiperfibrinogenemy [8]. In the case
of hypercoagulability, fibrinolysis process decides
about the scale of clinical symptoms of disorders of
the hemostasis. An analysis of the available literature shows that in patients with obesity the inhibition of fibrinolysis depending on high PAI-1 concentration is observed [9]. We did not find similar
research about fibrinolysis process in patients with
morbid obesity, pose one coming from our centre
made in a small number of patients (20) [10].
The aim of this study was to assess the chosen parameters of the fibrinolysis process in patients with BMI passing 40, classified for the surgical treatment of obesity.
Material and Methods
A total of 50 patients with morbid obesity were
included in the study. Patients were treated in the
Department of Surgery and Endocrinology dr A. Jurasz University Hospital in Bydgoszcz. The mean
803
PAI-1 and α2-AP in Patients with Morbid Obesity
age of the patients was 38.5 years. The examined
group consisted of 30 females and 20 males. The
mean body mass index (BMI) was 48.5; the mean
waist circumference was 128 cm. 12 patients were
smokers. In 19 sick people, an arterial hypertension appeared, 26 patients had type 2 diabetes, and
6 suffered from manifestations of thrombosis. The
control group consisted of 20 healthy volunteers
with correct BMI values (20–25) in the mean age
of 38 years.
Venous blood from patients and volunteers
was collected in a fasting state. The blood samples
were centrifuged. The concentration of tissue plasminogen activator (tPA:Ag), antigen of the plasminogen activator inhibitor type-1 (PAI-1:Ag),
D-dimers were measured in obtained platelet-poor
plasma. The concentration of these parameters was
determined by Enzyme Linked Immunosorbent
Assay (ELISA), PAI-1:Ag with American Diagnostika test made in Stamford, USA, normal values
3–43 ng/mL. T-PA:Ag and D-dimers were measured with Stago reagents made in France. Normal
values for D-dimers < 500 ng/mL. The concentration of fibrinogen was marked spectrofluorometric
method with Folin and Ciaocalteu reagents, normal values 2.0–4.5 g/L. The concentration of plasminogen and antiplasmin activity were performed
in an automated coagulometr CC-3003 apparatus
and reagents produced by Bio-Ksel Co, Poland.
Normal values for plasminogen: 50–150% and
a2-antiplasmin activity: 80–120%.
The research was approved by the Bioethics
Committee of Collegium Medicum in Bydgoszcz,
The Nicolaus Copernicus University in Torun
(no. KB/425/2007).
Table 1. Characteristics of selected clinical parameters in
patients with morbid obesity and the control group
Tabela 1. Charakterystyka wybranych parametrów klinicznych w grupie chorych z otyłością oraz w grupie
kontrolnej
Study
group
Control
group
Age [years]
38.54
38.2
High [cm]
169.96
167.5
Mass [kg]
140.5
63.3
BMI [kg/m2]
48.5
22.6
Smoking
12
0
Hypertension
19
0
Type 2 diabetes mellitus
26
0
Thrombosis symptoms
6
0
Statistical Analysis
Statistical analysis was performed with the use
of Statistica 8.0 software (StatStoft®). Shapiro-Wilk
test was used to assess the normality of the distribution. Testing of the normality of the distribution allowed us to use the classical t-Student test.
We have also used U-Mann-Whitney rank-sum
test when distribution was not normal. For varia­
bles, with normal distribution mean (X) and standard deviations (SD) were determined. The median (Me), lower quartile Q1 and upper quartile Q3
were used for values, which distribution was different from normal. The p-values < 0.05 were considered statistically significant.
Results
T-PA:Ag and PAI-1:Ag showed normal distribution, thus they were demonstrated with mean
(X) and standard deviations.
Fig. 1 shows the mean concentration of t-PA:Ag
in both groups. The higher value of t-PA:Ag was
observed in patients with morbid obesity (value
10.34 ng/mL) than in the control group, t-PA:Ag
value in control group was 4.78 ng/mL. The difference was statistically significant (p < 0.001).
Fig. 2 demonstrates the mean concentration of
PAI-1:Ag in both groups. The significant statistic difference was noted (p < 0.001). The concentration of
PAI-1 was 3 fold higher in patients (104.97 ng/mL)
compared to the control group (48.35 ng/mL).
The activity of the a2-antiplasmin and D-dimers concentration did not show normal distribution. They were demonstrated as median and
quartiles.
Fig. 3 registers the activity of the a2-antiplasmin
in patients and the control group. The activity of the a2-antiplasmin was significantly higher
in the study group compared with control group
(p < 0,001). a2-antiplasmin activity was 138% in
patients and 101% in control group.
Fig. 4 demonstrates the concentration of D-dimers in both groups. The concentration of D-dimers
was significant higher in patients (325.99 ng/mL)
compared with healthy persons (190.89 ng/mL).
No significant differentiation in fibrinogen
and plasminogen levels were observed between patients with morbid obesity and healthy volunteers.
The concentration of fibrinogen was 3.43 g/mL for
study group and 2.96 g/mL for the control group.
The concentration of plasminogen was 117.93% in
patients and 118.75% in the control group.
Table 2 Demonstrates BMI analysis according to additional factors that may influence fibrinolysis: smokers and non-smokers, diabetes and
804
M. Michalska et al.
Fig. 1. The mean concentration of t-PA:Ag in
the study group and the control group
16
14
Ryc. 1. Średnie wartości t-PA:Ag w osoczu krwi
osób otyłych i w grupie kontrolnej
t-PA:Ag [ng/ml]
12
10
p < 0.0001
8
6
mean
mean±SE
4
2
mean±SD
study group
grupa badana
control group
grupa kontrolna
Fig. 2. The mean concentration of PAI-1:Ag in
patients with morbid obesity and healthy volunteers
160
140
Ryc. 2. Średnie wartości PAI-1:Ag u osób
otyłych i w grupie kontrolnej
PAI-1:Ag [ng/ml]
120
100
p < 0.0001
80
60
mean
mean±SE
40
20
mean±SD
study group
grupa badana
control group
grupa kontrolna
Fig. 3. The activity of the a2-antiplasmin in
patients and control group
150
140
α 2 AP [%]
130
Ryc. 3. Mediana a2AP u osób otyłych i w grupie
kontrolnej
p < 0.0001
120
110
100
90
80
70
median
25%-75%
min-max
study group
grupa badana
control group
grupa kontrolna
hypertension. There were no significant differen­
ces in these subgroups.
BMI and the parameters of the fibrinolytic system correlations were not significant.
Discussion
The conducted study has shown that patients with morbid obesity have a higher concentration of t-PA:Ag, PAI-1:Ag and D-dimers with
a co-existing higher activity of a2-AP than healthy
volunteers.
Tissue plasminogen activator (t-PA) takes part
in keeping the fluidity of circulating blood. T-PA
is constitutive secreted by the endothelial cells,
where it is synthesized [11]. In physiological conditions the release of the t-PA into the blood increases in response to stress, physical activity, hypoxia,
venostasis [12]. In plasma the t-PA concentration
changes within 24 h increases in a day; however, it
is reduced at night. The level of t-PA antigen ri­ses
with age, is higher in men than in women. The increased level of this factor was observed in some
cancers: breast cancer, prostate cancer or lung cancer [13]. The increased t-PA:Ag concentration was
805
PAI-1 and α2-AP in Patients with Morbid Obesity
Fig. 4. The concentration of D-dimers in the
study and control group
1000
900
Ryc. 4. Stężenie D-dimerów u osób otyłych
i w grupie kontrolnej
D-dimer [ng/ml]
800
700
600
500
p < 0.01
400
300
200
median
25%-75%
min-max
100
0
study group
grupa badana
control group
grupa kontrolna
Table 2. BMI according to clinical factors
Tabela 2.Wartość wskaźnika BMI w zależności od czynników klinicznych
N
M ± SD
P
Smoking
12
47.92 – 7.78
0.7792
Non-smoking
38
48.65 – 5.02
DM type 2
26
47.70 – 6.41
Without DM
type 2
24
49.19 – 4.83
Hypertension
19
48.58 – 4.99
Without hypertension
31
48.45 – 5.99
0.4907
0.9540
also shown in conducted studies: in overweight patients and with simple obesity [11, 13, 14]. Similar findings were noted by Adamczyk et al. in patients with morbid obesity [10]. Due to the fact
that the tissue plasminogen activator is produced
by the endothelial cells, its increased concentration in blood may suggest the stimulation or injury of the endothelium in patients with morbid
obesity. Wannamethea et al. studied 3640 men
with coro­nary artery disease and showed a negative correlation of the adiponectin concentration
(that is decreased in obese people) with t-PA:Ag in
the blood [14]. According to Yudkin et al. visceral
adipose tissue is responsible for chronic inflammation, which may lead to insulin resistance and endothelial dysfunction [15].
In physiological conditions plasminogen activator inhibitor, type-1 is the main factor regulating fibrinolysis (PAI-1) [15]. It is also acting as the
inflammatory mediator as well as is a proangioge­
nic factor. It is synthesized by the cells of the endothelium of the blood vessels and livers as well as
by megakaryocytes [16]. It has been affirmed that
among all inhibitors of fibrinolysis process, the
Table 3. Correlation coefficients of the fibrinolytic parameters with BMI
Tabela 3. Współczynnik korelacji analizowanych parametrów fibrynolizy ze wskaźnikiem BMI
Parametr
BMI
p
D-Dimers
0.1483
0.470
t-PA:Ag
0.3048
0.191
PAI-1:Ag
–0.1794
0.380
Plazminogen
–0.0822
0.678
a2AP
–0.1872
0.350
PAI-1 binds plasminogen activators with the highest affinity. PAI-1 levels are increased in atherosclerosis, heart failure; high concentrations are
associated with cancers, bacterial infections and
thrombosis. The PAI-1 concentration is increased
in people with simple obesity. The positive correlation between PAI-1 level and BMI was noted by
Bart et al. and Mutch et al. [17, 9]. In our study the
PAI-1 concentration was significant higher in patients with morbid obesity compared to the control group and its mean level was 105 mg/mL, so
3 fold higher than in healthy people. Adamczyk et
al, Sola et al., Vazquez et al. obtained similar results [10, 18, 19]. The high concentration of PAI1 associated with obesity probably contributes to
the increased risk of cardiovascular disease. Due to
the fact of the 3 fold higher level than in healthy
people, it causes the decline in fibrinolytic activity because of the connection with t-PA. Data from
the literature shows that PAI-1 is produced by the
cells of adipose tissue, particularly the abdominal
cavity [20, 21].
Abdominal adipose tissue cells, known as
a major endocrine organ, secrete adipokines that
are responsible for the regulation of body weight.
Effects of leptin, which reduces appetite by the
806
M. Michalska et al.
hypothalamus and increases energy expenditure
and demonstrates high level in obese people, have
been relatively well-understood. Its concentration in obese people is low. Leptin effect has been
shown in the transcription and translation of the
PAI-1 and increased platelet ADP-dependent aggregation [23]. Alessi et al. suggest that PAI-1 concentration in metabolic syndrome depends on leptin, but also is stimulated by TNF-a and TGF-b
produced in visceral fatty tissue [24]. PAI-1 considered as a proangiogenic factor may be involved
in angiogenesis observed in patients with morbid
obesity.
The a2-antiplasmin (a2-AP) is another factor participating in the fibrinolysis process. It is
the main physiological inhibitor of plasmin which
creates complexes with plasmin in ratio 1 : 1. The
synthesis of this factor occurs in the liver as well
as in the kidneys [22]. Its decreased concentration appears in cirrhosis, DIC, amyloidosis, during childbirth, thromboclastic treatment and after operations. The decline in a2-AP activity can
provide a lowered production by hepatocytes or
increased expenditure during the creation of the
connection with plasmin in fibrinolysis activation
conditions. Świątkowska-Stodulska did not mention the increased concentration of a2-AP in obese
patients (BMI > 30) [8]. In our study the increase
in the a2-AP level in patients with morbid obesity (BMI > 40) is essential statistically relay to the
control group. The increasing activity of a2-AP in
plasma occurs during pregnancy and confinement.
It was shown that a2-AP participates in tissue remodeling [23], influences transforming growth
factor (TGF-β) production [24]. During pregnancy
an intensive reconstruction of the womb and placenta take place, as well as intense angiogenesis associated with the coming into existence of the foetus. Although there are no direct studies, it seems
that a2-antiplasmin could be the factor involved in
the reconstruction of tissues and angiogenesis in
patients with morbid obesity.
D-dimers are formed during stabilized fibrin
(the final product of coagulation process) digestion
by plasmin. The level of D-dimers can be helpful
in the diagnostic of DIC, deep venous thrombosis
or pulmonary embolism. In our study the concentration of D-dimers was statistically significantly
higher in patients with morbid obesity than in the
healthy volunteers. This fact suggests secondary
activation of fibrinolysis process in patients with
morbid obesity.
Conducted analysis of the additional factors as
arterial hypertension, diabetes or smoking (apart
from obesity) with a potential influence on the fibrinolysis did not demonstrate their participation in
fibrinolysis process disorders. The group of patients
with a high BMI greater than 40, and thus relatively homogeneous in terms of energy management
was the limitation of the present study. Limitations
of this study may also be associated with a greater number of women than men. These are young
women did not take into account the phase of the
menstrual cycle, which may affect the fibrinolytic
activity of blood. The relationship between fibrinolytic activity and age were not considered. It is important considering the known decreasing activity
of the fibrinolytic system with age.
In conclusion, the observed abnormalities in fibrinolysis system are connected with blood hypercoagulability in patients with morbid obesity, acting as an intravascular compensation mechanism.
Very high levels of PAI-1 are not only the result
of its release from platelets during microthrombosis, but also the result of its production by visceral
adipose tissue. Adipokines released by adi­pocytes
stimulates its formation in the liver. On the other
hand, PAI-1 as proangiogenic factor enhances the
proliferation of adipocytes that may be supported
by a2-antiplasmin.
The authors concluded that the conducted
study demonstrates that the activation of the fibrinolysis process was secondary for the coagulation
process, expressed with an increase in the t-PA:Ag
concentration and D-dimers concentration in patients with morbid obesity. The essential growth of
PAI-1:Ag level and a2-AP level shows strong inhibition of fibrinolysis in patients.
References
[1] World Health Organization. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation
presented at: the World Health Organization. June 3–5, 1997, Geneva, Switzerland.
[2] Owecki M: Otyłość epidemią XXI wieku. Przegl Kardiodiabetol 2009, 4, 36–41.
[3] Biela U, Pająk A, Kaczmarczyk-Chałas K: Częstość występowania nadwagi i otyłości u kobiet i mężczyzn w wieku
20–74 lat. Wyniki programu WOBASZ. Kardiol Pol 2005, 63, 6 (supl. 4).
[4] Szymocha M, Bryła M, Maniecka –Bryła I: Epidemia otyłości XXI wieku. Zdr Publ 2009, 119, 207–212.
[5] Boden G: Role of free fatty of the acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997, 46,
3–10.
[6] Kidalska I, Popławska-Kita A, Tejko B: Otyłość a zaburzenia przemiany materii. Zaburz Przem Mat 2006, 2,
94–101.
[7] Kołacz E, Giełwanowska L: Zaburzenia układu fibrynolizy w otyłości. Acta Haematol Pol 2003, 34, 325–330.
PAI-1 and α2-AP in Patients with Morbid Obesity
807
[8] Światkowska-Stodulska, Kazimierska E, Sworczak K: Zaburzenia hemostazy u osób otyłych. Wiad Lek 2007, 60, 3–4.
[9] Flegal KM, Graubard BI, Williamson DF, Gail MH: Excess deaths associated with underweight, overweight, and
obesity. JAMA 2005, 293, 1861–1867.
[10] Surgeman HJ, Wolfe LG, Sica DA: Diabetes and hypertension in severe obesity and effect of gastric bypassinduced weight loss. Ann Surg 2003, 237, 751–756.
[11] Much NJ, Wilson HM, Booth NA: Plasminogen activator inhibitor-1 and haemostasis in obesity. Proc Natr Soc
2001, 60, 341–347.
[12] Adamczyk P, Szafkowski R, Rość D: Tkankowy aktywator plazminogenu (t-PA) i inhibitor aktywatora plazminogenu typu-1 (PAI-1) w otyłości ogromnej. Med Biol Sci 2007, 21, 31–36.
[13] Van Guilder GP, Hoetzer GP, Smith HM: Endothelial t-PA release is impaired in overweight and obese adults
but can be improved with regular aerobic exercise. Am J Physiol Endocrinol Metab 2005, 289, E807–E813.
[14] Wannametee SG, Tchernowa J, Whincup P: Associations of adiponectin with metabolic and vascular risk parameters in the Brithish Regional Heart Study reveal stronger links to insulin resistance – related than to coronary heart
disease risk-related parameters. Internationals Journal of Obesity, 2007, 31, 1089–1098.
[15] Yudkin JS, Stehouwer CDA, Emeis JJ: C-reactive protein in healthy subjects: associations with obesity, insulin
resistance and endothelial dysfunction: a potential role for cytokines originating from adipose tissue. Arterioscler
Thromb Vasc Biol 1999, 19, 972–978.
[16] Takada A, Takada Y, Urano T: The physiological aspects of fibrinolysis. Thromb Res 1994, 76, 1–34.
[17] Rość D, Drewniak W, Kinasz-Różycka I: Trombomdulina, czynnik von Willebranda i tkankowy aktywator plazminogenu w osoczu krwi otyłych kobiet i mężczyzn. Pol Merk Lek 2003, 15, 90, 518.
[18] Svendsen OL, Hasseger Ch, Christiansen C: Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: effect of dieting with or without exercise in overweight postmenopausal women. Arterioscler
Thromb Vasc Biol 1996, 16, 381–385.
[19] Cierniewski CS: Postępy wiedzy o regulacji fibrynolizy. Acta Haematol Po 1994, 25, 15–26.
[20] Gils A, Declerc PJ: Plasminogen activator inhibitor-1. Curr Med Chem 2004, 11, 2323–2334.
[21] Bart M De Taeye, Novitskaya T, Gleaves L: Bone marrow plasminogen activator-1 influences the development of
obesity. J Biol Chem 2006, 281, 32796–32806.
[22] Sola E, Vaya A, Espana F: Plasminogen activator-1 levels in severe and morbid obesity. Effect of weight loss and
influence of 4G/5G polymorphism. Thromb Res 2008, 122, 320–327.
[23] Hou JZ, Okada K, Okamoto CH: Alpha-2 antiplasmin is a cristal regulator of angiogenin II mediated vascular
remodelling. Arterioscler Thromb Vasc Biol 2008, 28: 000–000.
[24] Allessi MC, Juhan-Vague I: PAI-1 and the metabolic syndrome: links, causes, and consequences. Artherioscler
Thromb Vasc Biol 2006, 26, 2200–2207.
[25] Vazquez LA, Pazos L, Barrazueta JR: Effects of changes in body weight and insulin resistance on inflammation
and endothelial function in morbid obesity after bariatric surgery. J Clin Endocrinol Metab 2005, 90, 316–322.
[26] Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004, 89, 2548–2556.
[27] Skowrońska B, Fichna M, Fichna P: Rola tkanki tłuszczowej w układzie dokrewnym. Endokrynologia, Otyłość
i Zaburzenia przemiany Materii 2005, 1, 21–29.
Address for correspondence:
Małgorzata Michalska
Department of Pathophysiology
Collegium Medicum in Bydgoszcz
Marii Skłodowskiej-Curie 9
85-094 Bydgoszcz
Poland
Tel. +48 52 585 35 91
E-mail: [email protected]
Conflict of interest: None declared
Received: 29.02.2012
Revised: 18.06.2012
Accepted: 26.11.2013