Ewa Wypasek

Publications of Ewa Wypasek

• Adiponectin, leptin, and resistin in patients with aortic stenosis without concomitant atherosclerotic vascular disease.

  Authors: Renata Kolasa-Trela, Tomasz Miszalski-Jamka, Grzegorz Grudzień, Ewa Wypasek, Magdalena Kostkiewicz

  Polskie Archiwum Medycyny Wewnętrznej. 09/2011; 121(10):352-59.

  Early stages of atherosclerosis and aortic stenosis (AS) are similar. Advanced coronary artery disease is characterized by altered profile of circulating adipocytokines. We hypothesized that plasmaEarly stages of atherosclerosis and aortic stenosis (AS) are similar. Advanced coronary artery disease is characterized by altered profile of circulating adipocytokines. We hypothesized that plasma profile of adipocytokines is associated with the severity of AS. The aim of the study was to evaluate the relationship between AS and adipocytokines. In 74 patients with AS without atherosclerosis and left ventricular ejection fraction above 50% (57 men, 17 women, aged 58 ±9.1 years) and 74 controls, resistin, leptin, and adiponectin levels were determined by the Bio-Rad Luminex system. Aortic valve area indexed to body surface area (AVAI) as well as the mean and peak transvalvular pressure gradients (PG) were assessed by echocardiography. We observed similar adiponectin and leptin levels in patients with AS and controls (20.8 ±7.9 vs. 20.4 ±3.9 μg/ml, P = 0.67 and 17.0 ±6.4 vs. 16.4 ±5.9 ng/ml, P = 0.52, respectively). Twenty-one patients had mild, 21 moderate, and 32 severe AS. After adjusting for age and the body mass index, adiponectin levels were 20.3 ±0.5 μg/ml in controls, 26.7 ±0.9 μg/ml in mild, 20.2 ±0.9 μg/ml in moderate, and 17.5 ±0.7 μg/ml in severe AS (P <0.001). Leptin levels were 16.4 ±0.7 ng/ml in controls, 21.1 ±1.3 ng/ml in mild, 16.9 ±1.3 ng/ml in moderate, and 14.4 ±1.1 ng/ml in severe AS (P = 0.003). Adiponectin and leptin correlated with the AVAI (r = 0.70, P <0.001; r = 0.37, P = 0.001; respectively), mean PG (r = -0.72, P <0.001; r = -0.27, P = 0.009; respectively), and peak PG (r = -0.67, P <0.001; r = -0.23, P = 0.03; respectively). In a multivariable analysis, the mean PG was the only independent echocardiographic predictor of adiponectin levels (P <0.001), while the AVAI was the only independent echocardiographic predictor of leptin levels in AS patients (P = 0.049). Lower levels of adiponectin and leptin, but not resistin, are associated with severe AS, suggesting that adipocytokines may be involved in the progression of AS, and especially adiponectin, which plays a protective role in this process.

• Does Diabetes Accelerate the Progression of Aortic Stenosis through Enhanced Inflammatory Response within Aortic valves?

  Authors: Joanna Natorska, Ewa Wypasek, Grzegorz Grudzień, Dorota Sobczyk, Grzegorz Marek, Grzegorz Filip, Jerzy Sadowski, Anetta Undas

  Inflammation. 09/2011;

  Diabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients withDiabetes predisposes to aortic stenosis (AS). We aimed to investigate if diabetes affects the expression of selected coagulation proteins and inflammatory markers in AS valves. Twenty patients with severe AS and concomitant type 2 diabetes mellitus (DM) and 40 well-matched patients without DM scheduled for valve replacement were recruited. Valvular tissue factor (TF), TF pathway inhibitor (TFPI), prothrombin, C-reactive protein (CRP) expression were evaluated by immunostaining and TF, prothrombin, and CRP transcripts were analyzed by real-time PCR. DM patients had elevated plasma CRP (9.2 [0.74-51.9] mg/l vs. 4.7 [0.59-23.14] mg/l, p = 0.009) and TF (293.06 [192.32-386.12] pg/ml vs. 140 [104.17-177.76] pg/ml, p = 0.003) compared to non-DM patients. In DM group, TF-, TFPI-, and prothrombin expression within valves was not related to demographics, body mass index, and concomitant diseases, whereas increased expression related to DM was found for CRP on both protein (2.87 [0.5-9]% vs. 0.94 [0-4]%, p = 0.01) and transcript levels (1.3 ± 0.61 vs. 0.22 ± 0.43, p = 0.009). CRP-positive areas were positively correlated with mRNA TF (r = 0.84, p = 0.036). Diabetes mellitus is associated with enhanced inflammation within AS valves, measured by CRP expression, which may contribute to faster AS progression.

• Effect of the E-selectin gene polymorphism (S149R) on platelet activation and adverse events after coronary artery surgery.

  Authors: Ewa Stępień, Sylwia Krawczyk, Bogusław Kapelak, Robert Sobczyński, Jarosław Stoliński, Ewa Wypasek, Anetta Undas, Jerzy Sadowski

  Archives of medical research. 08/2011; 42(5):375-81.

  A common single nucleotide polymorphism in the E-selectin (SELE) gene S149R results in the loss of E-selectin ligand binding specificity. The 149R allele has been associated with severeA common single nucleotide polymorphism in the E-selectin (SELE) gene S149R results in the loss of E-selectin ligand binding specificity. The 149R allele has been associated with severe cardiovascular diseases. We hypothesized that S149R may regulate platelet activation after stimuli associated with perioperative procedures in patients undergoing isolated coronary artery bypass grafting (CABG). Associations between the S149R polymorphism and an increased risk of perioperative acute thrombotic events with regards to a platelet count and activity were analyzed. In elective CABG patients (n = 152) we analyzed associations between S149R polymorphism and an increased risk of perioperative acute thrombotic events with regard to platelet count and activity. The S149R SELE gene polymorphism was determined by real-time polymerase chain reaction. Platelet count and activation marker (β-thromboglobulin-βTG) were evaluated. Prevalence of the S149R genotypes was as follows: 81.8% (n = 121) of homozygotes (149SS), 15.5% (n = 23) of heterozygotes and 2.7% (n = 4) of homozygotes (149RR). The 149R allele carriers had significantly higher postoperative βTG levels than the homozygotes (97 [79-120] vs. 76 [66-91] IU/mL, p = 0.03). Sixteen patients had adverse events: myocardial infarction (n = 14), stroke (n = 1) and fatal pulmonary embolism (n = 1). Twelve patients were carriers of the 149R allele. Relative risk (RR) of postoperative adverse events in the 149R allele carriers was 2.03 with 95% CI (1.05-3.03). Postoperative platelet activation is related to the S149R polymorphism, which enhances the risk of adverse events after CABG.

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• Increased levels of bone remodeling biomarkers (osteoprotegerin and osteopontin) in hypertensive individuals.

  Authors: Ewa Stępień, Ewa Wypasek, Katarzyna Stopyra, Małgorzata Konieczyńska, Małgorzata Przybyło, Mieczysław Pasowicz

  Clinical biochemistry. 07/2011; 44(10-11):826-31.

  Osteoprotegerin (OPG) and osteopontin (OPN) are bone metabolism biomarkers which are involved in the regulation of vascular calcification processes and prediction of future adverse cardiacOsteoprotegerin (OPG) and osteopontin (OPN) are bone metabolism biomarkers which are involved in the regulation of vascular calcification processes and prediction of future adverse cardiac events. OPG, OPN levels and classic risk factors were determined in 130 asymptomatic and hypertensive subjects. Receiver operator characteristic (ROC) analysis was performed and the area under the curve (AUC) was calculated. The hypertensive subjects had elevated OPG, OPN, fibrinogen, CRP and fasting glucose levels in comparison to the normotensive ones. There were significant correlations between age, CRP and OPG. Multiple regression analysis showed that as well as inflammation (CRP), age and hypertension were predictors of increased OPG levels. OPN increase was correlated with CRP and glucose levels. The AUCs were similar for OPG and OPG biomarkers. Plasma OPG and OPN levels were significantly associated with inflammation and arterial hypertension. They might be useful as additional biomarkers for monitoring endothelial dysfunction and prognosis of cardiovascular diseases.

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• Ezetimibe combined with simvastatin compared with simvastatin alone results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients after acute coronary events.

  Authors: Anetta Undas, Andrzej Machnik, Daniel P Potaczek, Ewa Wypasek, Krzysztof Zmudka, Wieslawa Tracz

  Journal of cardiovascular pharmacology. 05/2011; 58(2):167-72.

  We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In anWe compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In an investigator-initiated, double-blind, placebo-controlled, randomized study, patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe (n = 26) or 40 mg/d of simvastatin + placebo (n = 28) administered for 2 months. Markers of coagulation (prothrombin fragments 1.2, thrombin-antithrombin complexes, free tissue factor pathway inhibitor), fibrinolysis [plasminogen activator inhibitor-1, clot lysis time (CLT)], platelet activation (soluble CD40 ligand, β-thromboglobulin, thromboxane B2), oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)], and inflammation (interleukin-6, interleukin-18, and interleukin-1β) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy. A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group. Both groups were similar with regard to demographics, risk factors, medications, and routine laboratory results. Inflammatory, coagulation, and platelet markers did not differ between both treatment groups at all time points. Reductions in low-density lipoprotein cholesterol, CLT, plasminogen activator inhibitor-1, and 8-iso-PGF2α were significantly greater (by 10%, 8.7%, 17.5%, and 22.4%) in the simvastatin + ezetimibe group after 1 month, with further decreases in CLT and 8-iso-PGF2α at 2 months (all P < 0.05). These changes were not associated with lipid and inflammatory parameters. In conclusion, compared with simvastatin alone, simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS, indicating that ezetimibe might exert cholesterol-independent actions in humans (NCT00725829).

• Fibrinogen Beta-Chain -C148T Polymorphism is Associated with Increased Fibrinogen, C-Reactive Protein, and Interleukin-6 in Patients Undergoing Coronary Artery Bypass Grafting.

  Authors: Ewa Wypasek, Ewa Stepien, Malgorzata Kot, Dariusz Plicner, Boguslaw Kapelak, Jerzy Sadowski, Anetta Undas

  Inflammation. 04/2011;

  The fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- andThe fibrinogen beta-chain (FGB) -C148T polymorphism is linked with plasma fibrinogen concentration in the general population. We examined whether the -C148T polymorphism is associated with pre- and early postoperative levels of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) in 243 consecutive patients undergoing coronary artery bypass grafting (CABG) surgery. Plasma inflammatory markers were measured prior to and 5-7 days after surgery. The -C148T polymorphism was analyzed with the restriction fragment-length polymorphism method. The genotype distribution was as follows: CC-142 (58%), CT-85 (35%), and TT-16 (7%). Carriers of the -148T allele had higher preoperative plasma fibrinogen (4.42 ± 0.14 vs. 4.07 ± 0.11 mg/L, p = 0.04) and CRP levels (7.49 ± 1.2 vs. 4.26 ± 1.0 mg/L, p = 0.04) compared with non-carriers; 5 to 7 days after CABG, patients carrying -148T allele had increased CRP (70.4 ± 5.0 vs. 51.6 ± 4.25 mg/L, p = 0.005) and IL-6 levels (22.34 ± 2.64 vs. 15.53 ± 2.28 pg/L, p = 0.05), but not fibrinogen, compared with the remaining subjects. In-hospital nonfatal stroke occurred more frequently in -148T allele carriers (4% vs. 0%, p = 0.02). No genotype-associated differences were found in the occurrence of postoperative myocardial infarction and death. Presence of the -148T allele has also been associated with longer intensive care stay and intubation time (p = 0.01). Multivariate analysis identified the CT+TT genotype as an independent predictor of pre- and postoperative CRP levels. The results indicate that the presence of the -148T FGB allele determines higher pre- and postoperative levels of inflammatory markers, which might be associated with in-hospital clinical outcomes.

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• Morphine-modulated mast cell migration and proliferation during early stages of zymosan-induced peritonitis in CBA mice.

  Authors: Ewa Wypasek, Joanna Natorska, Elzbieta Stankiewicz, Elzbieta Kolaczkowska

  Folia biologica. 01/2011; 59(3-4):99-106.

  We have previously shown that supplementation of inflammation-inducing zymosan with a high dose ofmorphine inhibits peritoneal influx ofleukocytes in Swiss, C57C3H, Balb/c, and C57BL/6 strains butWe have previously shown that supplementation of inflammation-inducing zymosan with a high dose ofmorphine inhibits peritoneal influx ofleukocytes in Swiss, C57C3H, Balb/c, and C57BL/6 strains but not in CBA mice. We have also reported that the different pattern of the response to morphine treatment might be, at least partially, due to the inter-strain differences in the peritoneal mast cell (P-MC) number (high in CBA mice versus other strains) and P-MC specific features (high sensitivity to degranulation upon morphine treatment in CBA mice). The aim of the present study was to investigate the mechanism of morphine action on P-MC in CBA mice. In particular, the effects of morphine on the proliferation and migration of P-MC in CBA mice with ongoing zymosan-induced peritonitis modulated by morphine were studied. Morphine alone acted as a strong chemoattractant for P-MC of CBA mice and this effect was opioid receptor-independent. Moreover, flow cytometric analysis showed that i.p. morphine injection induced significant proliferation of P-MC in CBA mice. Therefore, we conclude that the lack of anti-inflammatory effects of morphine during peritonitis in CBA mice might result not only from a unique sensitivity of CBA mast cells to morphine-induced degranulation but also from the fact that mast cell numbers increase at the inflammatory focus. The latter might be due to morphine-induced mast cell proliferation and/or migration.

• Shorter preoperative fibrin clot lysis time predisposes to higher chest tube drainage in patients undergoing elective coronary artery bypass grafting surgery.

  Authors: Anetta Undas, Ewa Wypasek, Bogusław Kapelak, Jerzy Sadowski

  Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis. 06/2010; 21(4):380-1.

• [Optimalisation of treatment with vitamin K antagonists--the role of gene polymorphisms].

  Authors: Ewa Stępień, Ewa Wypasek, Agnieszka Branicka, Anetta Undas

  Kardiologia polska. 01/2010; 68 Suppl 5:S428-35.

  The magnitude of a maintenance vitamin K antagonist (VKA) dose during anticoagulant therapy depends not only on clinical, environmental, and demographic factors, but also on genetic factors. KnownThe magnitude of a maintenance vitamin K antagonist (VKA) dose during anticoagulant therapy depends not only on clinical, environmental, and demographic factors, but also on genetic factors. Known genetic polymorphisms explain 40-50% of the variance in VKA dosing. Polymorphisms of two genes encoding enzymes involved in vitamin K and/or VKA metabolism such as vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 isoform (CYP2C9) play a key role in this variance. Polymorphisms of cytochrome P450 4F2 isoform (CYP4F2), apolipoprotein E (APOE) and gamma-glutamyl carboxylase (GGCX) are of minor or negligible importance. In European populations, 3 haplotypes of VKORC1, VKORC1*2, VKORC1*3 and VKORC1*4--have been identified and they determined 99% of genetic variability of this enzyme. The presence of -1639G > A VKORC1 polymorphism is associated with increased VKA dose requirements. Allelic variants of CYP2C9*2 and CYP2C9*3 (found in 8-12% and 3-8% of individuals, respectively) increase the risk of haemorrhage due to slow VKA metabolism, especially at the therapy initiation. Pharmacogenetic algorithms incorporating VKORC1 and CYP2C9 genotypes help to predict the VKA dosage, particularly if the dose requirements are low or moderate. However, there is no compelling evidence showing reduced risk for clinical adverse events during VKA therapy following the identification of the patient's genetic profile.

• Residual iliofemoral thrombosis in a 31-year-old woman on oral contraceptives possessing heterozygous factor V Leiden, factor XIII Val34Leu allele and alpha-fibrinogen Thr312Ala allele: case report.

  Authors: Mariola Cieśla-Dul, Bogusław Gaweda, Ewa Wypasek, Maria Rózańska, Jerzy Sadowski

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):822-5.

  We present the case of a 31-year-old woman on oral contraceptives with a 3-year history of iliofemoral thrombosis resistant to recanalization despite satisfactory anticoagulation therapy and absenceWe present the case of a 31-year-old woman on oral contraceptives with a 3-year history of iliofemoral thrombosis resistant to recanalization despite satisfactory anticoagulation therapy and absence of concomitant diseases. Thrombophilia screening revealed heterozygous factor V Leiden mutation. We also detected the presence of factor XIII (FXIII) Leu34 allele and alpha-chain fibrinogen 312Ala allele, which are known to adversely affect fibrin clot structure and lysis. It might be speculated that the presence of 3 polymorphisms in this patient could contribute to proximal thrombosis resistant to treatment. We postulate that determination of FXIII and alpha-fibrinogen polymorphisms can be useful in the evaluation of some young patients with deep vein thrombosis.

• Factor XIII Val34Leu polymorphism and ischaemic stroke in patients with patent foramen ovale.

  Authors: Ewa Wypasek, Ewa Stepien, Monika Pieculewicz, Piotr Podolec, Anetta Undas

  Thrombosis and haemostasis. 12/2009; 102(6):1280-2.

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• Factor XIII Val34Leu polymorphism as a modulator of fibrin clot permeability and resistance to lysis in patients with severe coronary artery disease.

  Authors: Ewa Stępień, Dariusz Plicner, Bogusław Kapelak, Ewa Wypasek, Jerzy Sadowski, Anetta Undas

  Kardiologia polska. 08/2009; 67(8):947-955.

  Background: A common G to T transition in codon 34 with the subsequent valine with leucine replacement in the factor (F) XIII A-subunit affects fibrin formation and stabilisation in vitro. Data onBackground: A common G to T transition in codon 34 with the subsequent valine with leucine replacement in the factor (F) XIII A-subunit affects fibrin formation and stabilisation in vitro. Data on the effects of Leu34 allele on cardiovascular thromboembolic events in vivo are conflicting. Aim: We investigated 113 patients, aged 62.8 +/- 6.1 years, who were scheduled for elective isolated coronary artery bypass grafting surgery (CABG). Patients were compared with 98 healthy age-matched controls. Ex vivo fibrin clot permeability and lysis time (t50%) were determined in citrated plasma. Results: Patients scheduled for CABG had lower clot permeability (9.14 +/- 1.64 vs 10.02 +/- 1.12 x 10-9cm2; p = 0.0002) and longer t50% (8.45 +/- 1.94 vs 7.63 +/- 1.24 min; p < 0.0001) than controls. The Leu34 carriers, i.e. 9 (8%) Leu34Leu homozygous and 23 (20%) Val34Leu heterozygous subjects, had lower permeability by 23% in the CAD group compared with 81 (72%) patients with Val34Val genotype. A similar intergroup difference was observed for t50% which was longer in Leu34 carriers (p < 0.0001). The FXIII Leu34 allele on permeability and t50% was not affected by homocysteine, C-reactive protein and fibrinogen leveles in CAD patients and controls. Conclusions: Like in healthy subjects, in patients scheduled for CABG, the FXIII Leu34 allele is associated with decreased fibrin clot permeability and efficiency of lysis.

• Mast cells are responsible for the lack of anti-inflammatory effects of morphine in CBA mice.

  Authors: Elzbieta Stankiewicz, Ewa Wypasek, Barbara Plytycz

  Mediators of inflammation. 01/2005; 13(5-6):365-8.

  BACKGROUND AND AIM: Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. As peritoneal mast cells (pMCs) are much moreBACKGROUND AND AIM: Morphine co-injection has anti-inflammatory effects on zymosan-induced peritonitis in several strains of mice except that of CBA. As peritoneal mast cells (pMCs) are much more numerous in CBA mice than in SWISS mice, therole of pMCs in morphine-modulated zymosan peritonitis is compared in CBA and SWISS males. METHODS: pMCs were treated in vitro with morphine or C48/80 for comparison of histamine release. In vivo accumulation of leukocytes and histamine in peritoneal exudate were recorded after intraperitoneal injection with morphine, zymosan, or zymosan plus morphine. RESULTS AND CONCLUSION: Morphine induces histamine release by pMCs from CBA mice but not SWISS mice. In vivo morphine-induced peritonitis is stronger in CBA mice than SWISS mice. Corollary, morphine anti-inflammatory effects on zymosan peritonitis are reversed in CBA mice by its pro-inflammatory action through CBA pMCs.

• Quantification of airborne birch (Betula sp.) pollen grains and allergens in Krakow.

  Authors: Jacek Madeja, Ewa Wypasek, Barbara Plytycz, Krzysztof Sarapata, Krystyna Harmata

  Archivum immunologiae et therapiae experimentalis. 53(2):169-74.

  INTRODUCTION: Birch (Betula sp.) pollen grains are the main cause of seasonal allergies in northern and central Europe. The allergen particles released from the grains are often well distributed inINTRODUCTION: Birch (Betula sp.) pollen grains are the main cause of seasonal allergies in northern and central Europe. The allergen particles released from the grains are often well distributed in the air. Due to their size, airborne protein particles can easily penetrate into the lower parts of the respiratory airways and may lead to symptoms of asthma. The purpose of this paper was to quantify both Betula sp. pollen grains and allergens in the air. MATERIAL/METHODS: Materials for the investigation were collected in the spring of 2003 with two Hirst-type pollen volumetric traps. Tapes from one trap served for routine birch pollen grain counts, while those from the second for the immunodetection of birch allergens. As birch pollen allergen concentration is seen as dark spots on X-ray films densitometric measurements of the spots were used to quantify birch-pollen antigen concentrations in the air. RESULTS: In most instances, birch pollen counts corresponded with birch pollen allergen levels. However, on several occasions outside the pollen season, only grains or only allergens were detected. Apart from sampling variability, this could be due to faulty/dead pollen grains or submicronic airborne allergen particles. CONCLUSIONS: Counting intact pollen grains and antibody-based detection of allergen molecules are efficient tools in controlled allergen avoidance.