- Email: [email protected]
P53 CARDIOPROTECTIVE EFFECT OF RED WINE
78th EAS Congress
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
and markers of inflammation, adipocytokines, markers of oxidative stress and endothelial dysfunction. Results: When compared with controls, the subgroup of obese men had significantly higher values of oxLDL/beta2GPI, oxLDL and AOPP (all p < 0.01), however in regression analysis only oxLDL/beta2GPI correlated with the immunokine- IL-8 and endothelial dysfunction marker-PAI-I (both p < 0.01). Multiple regression analysis revealed that the correlation of oxLDL/beta2GPI with PAI-I remained significant independently of triglycerides, BMI and WHR. Conclusion: In early-stage of insulin resistance, plasma concentration of the oxLDL/beta2GPI complex reflects both inflammation and endothelial dysfunction. Increased oxLDL/beta2GPI may thus serve as a marker of atherosclerosis initiation on the endothelium level. Supported by MSM0021620814. P49 AN ERYTHROPOIETIN RECEPTOR (EPOR) IN HUMAN ADIPOSE TISSUE (AT) 1 1 K. Moller ¨ 1 , E. Piella2 , P. Algenstaedt2 , D.E. Muller-Wiefel ¨ . Pediatric Nephrology, Children’s Hospital of the University of Hamburg, 2 Endocrinology, Medical Clinic of the Universitiy of Hamburg, Hamburg, Germany
AT is an endocrine organ − secreting inflammatoric and antiinflammatoric adipocytokines playing an important role in the development of atherosclerosis. However, few is known about the regulation of the expression of adipocyte derived products. The observation that renal patients under therapy with an erythropoietin stimulation factor (ESF) have higher serum-adiponectine concentrations than those without therapy leads to the hypothesis that there might be a tissue specific EPOR in AT. We investigated the expression of an EPOR in human AT under the influence of ESF. AT of patients was harvested during an elective surgery. Probes were incubated with ESF vs simple culture medium. The m-RNA of the adipocytes was isolated, a relative quantification by real-time PCR and the sequencing of all three domains of the EPOR was performed. The EPOR and the phosphorylation of Stat5 and Jak2 on protein level were examined by Western blot technique. The expression of an EPOR on RNA and protein level could be demonstrated in AT. After stimulation with ESF there was an increase of mRNA-expression of the EPOR and an increase of the expression of phosphorylated Jak2 and Stat5. Data show for the first time an expression of an EPOR in human AT and its regulation by ESF. Therefore a direct influence of ESF on the regulation of the expression of adipocytokines in human AT can be assumed. The EPOR could be an important factor in the regulation of the endocrine functions of AT and might play a protective role in the development of atherosclerosis. P50 VARIANT IN KIF6 PREDICTS CORONARY EVENTS AND EVENT REDUCTION FROM STATIN THERAPY: CARE, WOSCOPS, PROSPER AND PROVE IT-TIMI 22 STUDIES O. Iakoubova. Cardiovascular Diseases, Celera, Alameda, CA, USA Aims: To identify and validate genetic variants associated with risk for coronary events and differential response to statin therapy, we investigate the association between a 719Arg variant of kinesin family member 6 (encoded by the gene KIF6) and coronary events in placebo groups of CARE and WOSCOPS and response to statin therapy in the CARE, WOSCOPS, PROSPER and PROVE IT-TIMI 22 trials. Results: In placebo-treated patients, carriers of the KIF6 719Arg allele (59% of population) had a hazard ratio of 1.50 (95% CI 1.05–2.15) in CARE, an odds ratio of 1.55 (95% CI 1.14–2.09) in WOSCOPS, and a hazard ratio of 1.28 (95% CI 0.98–1.69) in PROSPER patients with prior vascular disease. Among 719Arg carriers, the absolute risk reduction from pravastatin therapy was 4.9% (95% CI 1.8−8.0) in CARE, 5.5% (95% CI 3.5−7.5) in WOSCOPS, and 6.3% (95% CI 2.5–10.0%) in PROSPER patients with prior vascular disease. In contrast, no significant risk reduction was observed among noncarriers in any of these studies. In PROVE IT-TIMI 22, benefit from high-dose, compared with standard-dose, statin therapy was significantly greater in carriers (p = 0.018 for interaction between 719Arg carrier status and treatment) with an absolute risk reduction of 10.0% (95% CI 4.9–15.0%) in carriers versus 0.8% in noncarriers. In conclusion, we have idenified a KIF6 719Arg variant that predicts risk of coronary events and event reduction during pravastatin therapy. In addition, carriers also received significantly greater benefit (event reduction) from highdose statin therapy than noncarriers received. P51 HOMOCYSTEINE AS A CARDIOVASCULAR RISK MARKER IN POLYCYSTIC OVARY SYNDROME A. Atanasova1 , G. Dimitrov1 , S. Biljali2 . 1 University Clinic for Gynecology and Obstetric, 2 Institute for Clinical Chemistry, Skopje, FYR Macedonia Polycystic ovary syndrome (PCOS) is a condition characterized by oligomenorhea and androgen excess, affects 6−10% of the women in reproductive period. Although the pathogenesis is still uncertain, many studies suggest that PCOS may increase risk for several conditions
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including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular risk. Woman with PCOS would be expected to be at significantly increased risk for atherosclerotic disease. Hyperhomocysteinemia has been shown as independent predictor of cardiovascular mortality in patients with atherosclerosis. The aim of our study was to determinate levels of homocysteine in woman with polycystic ovary syndrome compared with healthy woman. Thirty two patients (age, 23.5±5.5) with PCOS and twenty five (age, 25.5±4.3) healthy woman were involved in the study. Blood samples were collected in early follicular phase. Total homocysteine was measured using fluorescent immunoassay. Statistically significant differences in serum concentration of homocysteine were observed between groups. Mean homocysteine level we found as (10.2±2.9 vs. 7.0±1.5) in PCOS and normal group respectively (p < 0.05). For Macedonian population we found statistically significant increased homocysteine levels in woman with PCOS. Although the mean homocysteine levels are within normal limits, there are significant higher mean homocysteine concentrations between these two groups. Because increased concentrations of tHcy has been shown as an independent risk factor for cardiovascular alterations, it is essential that in this group of woman are taken measures for early prevention. P52 INFLUENCE OF ARTERIAL STIFFNESS, BODY CONSISTENCY AND SECONDHAND SMOKE EXPOSURE ON CHRONIC VALVE DISEASE AND MYOCARDIAL INFARCTION A. Domonkos Tarnoki1 , D.L. Tarnoki1 , Z. Garami2 , G. Veress3 . 1 Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary, 2 Methodist Hospital DeBakey Heart and Vascular Center, Houston, TX, USA, 3 State Hospital of Cardiology, Balatonfured, Hungary Objective: Pulse Wave Velocity (PWVao) and Augmentation Index (AIxbra) are associated with the structural changes of arteriosclerosis but never investigated between the two subject groups. Aim: To determine the arterial stiffness, body consistency and secondhand smoke (SHS) exposure among patients suffering from chronic valve disease (CVD) and myocardial infarction (MI). Methods: 138 patients were examined (97 MI and 41 CVD) by TensioMed Arteriograph, OMRON BF500 body consistency monitor (via bioimpendance analysis) and a detailed questionnaire. Results: Higher Aixbra was found in MI group (0.85±25.5 vs. −2.9±31%). PWVao was higher in CVD group (12±3.2 vs. 11.2±2.5 m/s). PWVao and Aixbra worsen by aging in both groups. MI group had higher peripherial blood pressure (138/77 vs. 132/74 Hgmm), SBPao (137.7±22.5 vs. 130.3±19.3 Hgmm), MAP (97.6±11.6 vs. 93.19±9.2 Hgmm), decreased DRA (39.64±11.2 vs. 43.87±15.8) and DAI (46.4±9.7 vs. 52±7%), respectively. Higher BMI (29.19±4.6 vs. 27.54±3.7 kg/m2 ), body fat% (32.49±10.8 vs. 30.68±10.2%), visceral fat (12.3±4.3 vs. 10.41±3.9), smoking rate (52.6 vs. 46.3%) and duration (26.6 vs. 22.3 years), significant higher home, workplace and other SHS exposure (1.27 vs 0.45, 1.47 vs 1.03, 0.45 vs 0.27 hours/day) were present in MI group. Conclusions: Increased and abnormal arterial stiffnesses were found in both groups indicating presence of atherosclerosis. Adverse body consistency (higher body fat% and visceral fat) and higher SHS exposure indicate an increased risk of MI. P53 CARDIOPROTECTIVE EFFECT OF RED WINE A. Novakovic1 , L. Gojkovic Bukarica2 , D. Nezic3 , M. Peric3 , V. Kanjuh4 . 1 Dept. of Pharmacology, Faculty of Pharmacy, 2 Dept. of Pharmacology, School of Medicine, 3 Institute of Cardiovascular Diseases “Dedinje”, 4 Academy of Sciences and Arts, Belgrade, Serbia The lower incidence of coronary artery disease in the Soutern French and other Mediterranean populations, despite a diet rich in saturated fat and high smoking habits (the so-called French paradox), has been atributed to the prolonged and moderate red wine consumption by these population. It is considered that resveratrol, as a polyphenol, is presented in red wine in significant amounts, and partly responsible for cardiovascular benefits associated with wine consumption. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. Aim: The aim of this study was to investigate the mechanism (s) of resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) with endothelium and without endothelium. Methods: HIMA were precontracted with phenylephrine (10 mM). Results: Resveratrol induced a concentration-dependent relaxation of the rings with endothelium and without endothelium. Highly selective blocker of ATPsensitive K+ channels, glibenclamide as well as nonselective blockers of Casensitive K+ channels, tetraethylammonium did not block resveratrol-induced relaxation of HIMA rings. Charybdotoxin, a blocker of calcium-sensitive K+ channels did not affect the resveratrol-induced relaxation. 4-Aminopyridine, non selective blocker of voltage-gated K+ (KV ) channels, and margatoxin that inhibits KV 1 channels abolished relaxation of HIMA rings induced by resveratrol.
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Atherosclerosis Supplements 11, no. 2 (2010) 17–108
Conclusions: In conclusion, we have shown that resveratrol can induce relaxation of HIMA with endothelium and without endothelium It seems that 4-aminopyridine- and margatoxin-sensitive K+ channels located in vascular smooth muscle mediated relaxation of HIMA produced by resveratrol. P54 MATRIX METALLOPROTEINASE-9 (MMP-9), ITS TISSUE INHIBITOR TIMP-1 AND NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS NEW ATHEROSCLEROSIS MARKERS IN CHRONICALLY DIALYZED PATIENTS K. Musial, D. Zwolinska. Department of Pediatric Nephrology, Wroclaw Medical University, Wroclaw, Poland Background: Patients on chronic dialysis are prone to cardiovascular complications, being the first cause of morbidity and mortality. The MMP/TIMP proteolytic system may play an essential role in atherosclerosis, but the data concerning such influence in dialyzed patients are scarce. The aim of study was to assess concentrations of MMP-9 (gelatinase B) with anti-atherogenic activity, its specific inhibitor TIMP-1 and NGAL, preventing MMP-9 degradation by forming a dimer, in children and young adults on automated peritoneal dialysis (APD) and on hemodialysis (HD). Material and Methods: 22 children on APD, 17 patients on HD and 23 controls were examined. Serum concentrations of MMP-9, TIMP-1 and NGAL were assessed by ELISA. Serum CHOL, HDL-CHOL, LDL-CHOL, TGL and hsCRP were also evaluated. Results: Median values of MMP-9, TIMP-1, NGAL and MMP-9/NGAL ratio were significantly elevated in all dialyzed children vs. controls and were higher in HD than in APD. TIMP-1 values in HD exceeded 3 times those in APD. Consequently, the MMP-9/TIMP-1 ratio, although increased in APD (p < 0.00001) and HD (p < 0.01), was higher in APD than in HD (p < 0.00001). MMP-9 correlated with TGL in HD, TIMP-1 − with HDL-CHOL in HD and with hsCRP in APD. NGAL correlated with CHOL, HDL-CHOL and hsCRP in APD. Conclusions: Our results suggest the dysfunction of MMP/TIMP system in children on dialysis, with APD being less atherogenic than HD. Correlations with lipid profile and hsCRP may suggest the role of MMP-9, TIMP-1 and NGAL as new markers of atherosclerosis in the examined population. P55 THE TREATMENT OF COLESTERYL STORAGE DISEASE (CESD) BY EZETIMIBE MONOTHERAPY F. Abello1 , O. Guardamagna1 , V. Baracco1 , R. Bonardi2 . 1 Department of Pediatrics, 2 Department of Gastroenterology, University of Turin, Turin, Italy Objective: CESD is a rare lysosomal disorder affecting intrahepatic colesterol hydrolysis lacking a specific treatment. Ezetimibe, a cholesterol absorption inhibitor, should represent an option never delivered as monotherapy. Methods: A 15 yrs old male patient affected by CESD, diagnosed on the basis of liver steato-fibrosis and LIPA gene mutation, was treated with 10 mg/die for 2 yrs. Biochemical parameters were checked at basal time, 6 months, 1, 2 yrs since starting therapy. Liver enzymes, lipid profile were tested by standard methods. Inflammatory markers of lipid peroxidation interleukins 1beta (IL1b) and 6 (IL6) were evaluated using western blot analyses. Tranforming growth factor-beta1 (Tgf-beta1), choosen as hepatic fibrosis parameter was evaluated by elisa kit. The serum protein adducts Malonaldehyde (MDA) and 4-hydroxynonenal (HNE) were analyzed to test the oxidative damage. Liver elastograpy employed to test liver fibrosis. Results: Liver enzymes normalized by 6 months of therapy; total cholesterol and LDL-C decreased by 30% and 25% respectively at the same time. IL1b and IL6 decreased after one year of treatment. As well the oxidative markers malonaldehyde (MDA) and 4-hydroxynonenal (HNE) resulted 4.3±0.3 and 6.9±0.7 AFU/mg protein in basal condition and 3.8±0.5 and 5.1±0.5 AFU/mgprotein after 1 yr treatment, so showing a normal value. Tgfbeta1 did not change in agreement with unchanged elastografic fibrosis. Conclusion: Emphasis for CESD will lead to the disorder being recognized and correctly treated. Present results underline the well tolerated successful outcome reached by ezetimibe monotherapy in reducing lipoprotein levels, normalizing transaminases, cytokines and oxidative stress parameters. P56 INFLUENCE OF PHYSICAL TRAININGS ON BLOOD OXYGEN TRANSPORT INDICES AND ENDOTHELIAL FUNCTION IN PATIENTS WITH STABLE ANGINA L. Yankovskaya. Grodno State Medical University, Grodno, Belarus The aim of our study was to assess the efficiency of the medicinal treatment and bicycle trainings (BT) in patients with stable angina class II as for the indices of blood oxygen transport (BOT) and endothelial function. Group A included 16 patients which were treated with medicines. Group B included 10 patients which were treated with the same medicines plus BT for 14 days. BOT indices (pO2, pCO2, pH, Hb, metHb) were measured using microgas analyzer. The hemoglobin-oxygen affinity was determined according to the p50 index. Endothelium dependent vasodilatation (EDV) was measured by plethysmography. Plasma nitrite/nitrate level (NOx) was determined using Griess method.
Poster Presentations
Results: Maximally tolerated load increased only in group B by 27.8% (p < 0.05). The number of metabolic units also increased and was 7.80±0.47, which indicated improved assimilation of oxygen by tissues. “Double product”, indirectly characterizing assimilation of oxygen by myocardium, increased by 12.3% (p < 0.05) in group B and did not change in group A. Indices of BOT did not change, p50 increased in group A after treatment. In group B pO2 after treatment was 13.4% (p < 0.05) higher than in group A. pH increased to 7.334±0.009 units, p50 increased by 3.1% (p < 0.05). In group A EDV became 14.04±1.23% (p < 0.001). In group B EDV became 17.70±1.73% (p < 0.001) and was 26% higher, than in group A. NOx increased (p < 0.05) only in group B and was 21.81±1.09 mmol/l. Conclusion: BT improves more effectively oxygen supply of tissues and endothelial function as compared to medicinal treatment alone in patients with stable angina. P57 LIPO-RETRO-D-PEPTIDES: NEXT GENERATION OF THE HIGHMOST SELECTIVE THROMBIN INHIBITORS A. Poyarkov, S. Poyarkova. Protein Chemistry Department, Institute of Bioorganic Chemistry and Petrochemistry of the Ukrainian National Academy of Sciences, Kyiv, Ukraine The research is devoted to the investigation of structure–activity relationship (SAR) of novel inhibitors with a main target of the blood coagulation system enzyme-thrombin. Chemical modification of the main retro-D-peptide sequence − D-Arg-D-Pheby different aromatic, heterocyclic and aliphatic moieties led to discovery of lipo-retro-D-peptides − highmost selective thrombin inhibitors. Modification of the retro-D-peptide sequence − D-Arg-D-Phe- by fatty acids residues provided compounds which inhibit thrombin in the range of Ki from 2 to 0.1 mM and with selectivity of 200–6000 against trypsin. It has been proved that the well-known surfactant LAE (Na-Lauroyl arginine ethyl ester) is a competitive reversible thrombin inhibitor. It has been shown that LAE inhibits thrombin activity almost 20 times stronger than trypsin (Ki = 18.9 mM). At the same time LAE is hydrolyzed by thrombin at pH 8.5 (kcat = 3.6 c-1) and trypsin (kcat = 56 c-1) at the same pH. The LAE ability to activate plasmin at the same range of thrombin inhibition concentration deserves special attention. These findings establish an important role of fatty moiety in structure of inhibitors in preferential selective binding and inhibition of thrombin active side. Features of ion formation under the influence of laser emission under the conditions of MALDI-TOF mass spectrometry in the glycosylated protein thrombin and the related proteases trypsin and chymotrypsin were studied for the first time. In addition, the attempt to investigate features of thrombin-inhibitor interactions with MALDI TOF MS was made. P58 DETERMINATION OF THE PROOXIDANT–ANTIOXIDANT BALANCE IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY AND IN RENAL TRANSPLANT PATIENTS V. Markovic, T. Gojkovic, M. Kostic. University of Belgrade, Belgrade, Serbia Introduction: Several studies results indicate that oxidative stress might contribute to renal disease development. The aim of study: Determination of prooxidant–antioxidant balance (PAB) in patients with chronic renal insufficiency (HRI) and in renal transplant patients in purpose of identifying oxidative stress as risk factor in renal disease development. Methods and Material: Thirty-eight patients (12 patients with HRI and 26 renal transplant patients) and fifty healthy volunteers were chosen for this study. PAB, as indicator of oxidative stress state, was determined in plasma using spectrophotometric method. The absorbance of coloured compound, that is a product of reaction between 3,3 ,5,5 -tetramethylbenzidine and hydrogenperoxide, was read at 450nm. The results are expressed in HKU. Results: The results of this study indicate significant decreasing in antioxidative parameter values (enzyme SOD and SH-groups) of renal patients in comparison to control group, while the control group stated higher activity of antioxidative enzyme PON1. Increased values of SH-groups and decreased level of O−2 in patients with HBI indicate better antioxidative state in comparison to renal transplant patients. Significant increase of the PAB value was observed in renal patients in comparison to control group, but there was no significant difference betwen the two groups of patiens. In control group, positive corelation was found between PAB and leucocytes and negative corelation with enzym paraoxonase. Positive corelation between PAB and DZO in patients group probably represents a compensatory organism response. Conclusion: Measuring PAB might be useful for evaluation of oxidative stress state in patients with renal function failure.
Atherosclerosis Supplements 11, no. 2 (2010) 17–108
and markers of inflammation, adipocytokines, markers of oxidative stress and endothelial dysfunction. Results: When compared with controls, the subgroup of obese men had significantly higher values of oxLDL/beta2GPI, oxLDL and AOPP (all p < 0.01), however in regression analysis only oxLDL/beta2GPI correlated with the immunokine- IL-8 and endothelial dysfunction marker-PAI-I (both p < 0.01). Multiple regression analysis revealed that the correlation of oxLDL/beta2GPI with PAI-I remained significant independently of triglycerides, BMI and WHR. Conclusion: In early-stage of insulin resistance, plasma concentration of the oxLDL/beta2GPI complex reflects both inflammation and endothelial dysfunction. Increased oxLDL/beta2GPI may thus serve as a marker of atherosclerosis initiation on the endothelium level. Supported by MSM0021620814. P49 AN ERYTHROPOIETIN RECEPTOR (EPOR) IN HUMAN ADIPOSE TISSUE (AT) 1 1 K. Moller ¨ 1 , E. Piella2 , P. Algenstaedt2 , D.E. Muller-Wiefel ¨ . Pediatric Nephrology, Children’s Hospital of the University of Hamburg, 2 Endocrinology, Medical Clinic of the Universitiy of Hamburg, Hamburg, Germany
AT is an endocrine organ − secreting inflammatoric and antiinflammatoric adipocytokines playing an important role in the development of atherosclerosis. However, few is known about the regulation of the expression of adipocyte derived products. The observation that renal patients under therapy with an erythropoietin stimulation factor (ESF) have higher serum-adiponectine concentrations than those without therapy leads to the hypothesis that there might be a tissue specific EPOR in AT. We investigated the expression of an EPOR in human AT under the influence of ESF. AT of patients was harvested during an elective surgery. Probes were incubated with ESF vs simple culture medium. The m-RNA of the adipocytes was isolated, a relative quantification by real-time PCR and the sequencing of all three domains of the EPOR was performed. The EPOR and the phosphorylation of Stat5 and Jak2 on protein level were examined by Western blot technique. The expression of an EPOR on RNA and protein level could be demonstrated in AT. After stimulation with ESF there was an increase of mRNA-expression of the EPOR and an increase of the expression of phosphorylated Jak2 and Stat5. Data show for the first time an expression of an EPOR in human AT and its regulation by ESF. Therefore a direct influence of ESF on the regulation of the expression of adipocytokines in human AT can be assumed. The EPOR could be an important factor in the regulation of the endocrine functions of AT and might play a protective role in the development of atherosclerosis. P50 VARIANT IN KIF6 PREDICTS CORONARY EVENTS AND EVENT REDUCTION FROM STATIN THERAPY: CARE, WOSCOPS, PROSPER AND PROVE IT-TIMI 22 STUDIES O. Iakoubova. Cardiovascular Diseases, Celera, Alameda, CA, USA Aims: To identify and validate genetic variants associated with risk for coronary events and differential response to statin therapy, we investigate the association between a 719Arg variant of kinesin family member 6 (encoded by the gene KIF6) and coronary events in placebo groups of CARE and WOSCOPS and response to statin therapy in the CARE, WOSCOPS, PROSPER and PROVE IT-TIMI 22 trials. Results: In placebo-treated patients, carriers of the KIF6 719Arg allele (59% of population) had a hazard ratio of 1.50 (95% CI 1.05–2.15) in CARE, an odds ratio of 1.55 (95% CI 1.14–2.09) in WOSCOPS, and a hazard ratio of 1.28 (95% CI 0.98–1.69) in PROSPER patients with prior vascular disease. Among 719Arg carriers, the absolute risk reduction from pravastatin therapy was 4.9% (95% CI 1.8−8.0) in CARE, 5.5% (95% CI 3.5−7.5) in WOSCOPS, and 6.3% (95% CI 2.5–10.0%) in PROSPER patients with prior vascular disease. In contrast, no significant risk reduction was observed among noncarriers in any of these studies. In PROVE IT-TIMI 22, benefit from high-dose, compared with standard-dose, statin therapy was significantly greater in carriers (p = 0.018 for interaction between 719Arg carrier status and treatment) with an absolute risk reduction of 10.0% (95% CI 4.9–15.0%) in carriers versus 0.8% in noncarriers. In conclusion, we have idenified a KIF6 719Arg variant that predicts risk of coronary events and event reduction during pravastatin therapy. In addition, carriers also received significantly greater benefit (event reduction) from highdose statin therapy than noncarriers received. P51 HOMOCYSTEINE AS A CARDIOVASCULAR RISK MARKER IN POLYCYSTIC OVARY SYNDROME A. Atanasova1 , G. Dimitrov1 , S. Biljali2 . 1 University Clinic for Gynecology and Obstetric, 2 Institute for Clinical Chemistry, Skopje, FYR Macedonia Polycystic ovary syndrome (PCOS) is a condition characterized by oligomenorhea and androgen excess, affects 6−10% of the women in reproductive period. Although the pathogenesis is still uncertain, many studies suggest that PCOS may increase risk for several conditions
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including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular risk. Woman with PCOS would be expected to be at significantly increased risk for atherosclerotic disease. Hyperhomocysteinemia has been shown as independent predictor of cardiovascular mortality in patients with atherosclerosis. The aim of our study was to determinate levels of homocysteine in woman with polycystic ovary syndrome compared with healthy woman. Thirty two patients (age, 23.5±5.5) with PCOS and twenty five (age, 25.5±4.3) healthy woman were involved in the study. Blood samples were collected in early follicular phase. Total homocysteine was measured using fluorescent immunoassay. Statistically significant differences in serum concentration of homocysteine were observed between groups. Mean homocysteine level we found as (10.2±2.9 vs. 7.0±1.5) in PCOS and normal group respectively (p < 0.05). For Macedonian population we found statistically significant increased homocysteine levels in woman with PCOS. Although the mean homocysteine levels are within normal limits, there are significant higher mean homocysteine concentrations between these two groups. Because increased concentrations of tHcy has been shown as an independent risk factor for cardiovascular alterations, it is essential that in this group of woman are taken measures for early prevention. P52 INFLUENCE OF ARTERIAL STIFFNESS, BODY CONSISTENCY AND SECONDHAND SMOKE EXPOSURE ON CHRONIC VALVE DISEASE AND MYOCARDIAL INFARCTION A. Domonkos Tarnoki1 , D.L. Tarnoki1 , Z. Garami2 , G. Veress3 . 1 Department of Radiology and Oncotherapy, Semmelweis University, Budapest, Hungary, 2 Methodist Hospital DeBakey Heart and Vascular Center, Houston, TX, USA, 3 State Hospital of Cardiology, Balatonfured, Hungary Objective: Pulse Wave Velocity (PWVao) and Augmentation Index (AIxbra) are associated with the structural changes of arteriosclerosis but never investigated between the two subject groups. Aim: To determine the arterial stiffness, body consistency and secondhand smoke (SHS) exposure among patients suffering from chronic valve disease (CVD) and myocardial infarction (MI). Methods: 138 patients were examined (97 MI and 41 CVD) by TensioMed Arteriograph, OMRON BF500 body consistency monitor (via bioimpendance analysis) and a detailed questionnaire. Results: Higher Aixbra was found in MI group (0.85±25.5 vs. −2.9±31%). PWVao was higher in CVD group (12±3.2 vs. 11.2±2.5 m/s). PWVao and Aixbra worsen by aging in both groups. MI group had higher peripherial blood pressure (138/77 vs. 132/74 Hgmm), SBPao (137.7±22.5 vs. 130.3±19.3 Hgmm), MAP (97.6±11.6 vs. 93.19±9.2 Hgmm), decreased DRA (39.64±11.2 vs. 43.87±15.8) and DAI (46.4±9.7 vs. 52±7%), respectively. Higher BMI (29.19±4.6 vs. 27.54±3.7 kg/m2 ), body fat% (32.49±10.8 vs. 30.68±10.2%), visceral fat (12.3±4.3 vs. 10.41±3.9), smoking rate (52.6 vs. 46.3%) and duration (26.6 vs. 22.3 years), significant higher home, workplace and other SHS exposure (1.27 vs 0.45, 1.47 vs 1.03, 0.45 vs 0.27 hours/day) were present in MI group. Conclusions: Increased and abnormal arterial stiffnesses were found in both groups indicating presence of atherosclerosis. Adverse body consistency (higher body fat% and visceral fat) and higher SHS exposure indicate an increased risk of MI. P53 CARDIOPROTECTIVE EFFECT OF RED WINE A. Novakovic1 , L. Gojkovic Bukarica2 , D. Nezic3 , M. Peric3 , V. Kanjuh4 . 1 Dept. of Pharmacology, Faculty of Pharmacy, 2 Dept. of Pharmacology, School of Medicine, 3 Institute of Cardiovascular Diseases “Dedinje”, 4 Academy of Sciences and Arts, Belgrade, Serbia The lower incidence of coronary artery disease in the Soutern French and other Mediterranean populations, despite a diet rich in saturated fat and high smoking habits (the so-called French paradox), has been atributed to the prolonged and moderate red wine consumption by these population. It is considered that resveratrol, as a polyphenol, is presented in red wine in significant amounts, and partly responsible for cardiovascular benefits associated with wine consumption. The mechanism of cardiovascular benefits probably includes vasorelaxation, antioxidant and anti-platelet effects of resveratrol. The mechanisms by which resveratrol causes vasodilatation are uncertain. Aim: The aim of this study was to investigate the mechanism (s) of resveratrol-induced vasorelaxation in human internal mammary artery (HIMA) with endothelium and without endothelium. Methods: HIMA were precontracted with phenylephrine (10 mM). Results: Resveratrol induced a concentration-dependent relaxation of the rings with endothelium and without endothelium. Highly selective blocker of ATPsensitive K+ channels, glibenclamide as well as nonselective blockers of Casensitive K+ channels, tetraethylammonium did not block resveratrol-induced relaxation of HIMA rings. Charybdotoxin, a blocker of calcium-sensitive K+ channels did not affect the resveratrol-induced relaxation. 4-Aminopyridine, non selective blocker of voltage-gated K+ (KV ) channels, and margatoxin that inhibits KV 1 channels abolished relaxation of HIMA rings induced by resveratrol.
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Atherosclerosis Supplements 11, no. 2 (2010) 17–108
Conclusions: In conclusion, we have shown that resveratrol can induce relaxation of HIMA with endothelium and without endothelium It seems that 4-aminopyridine- and margatoxin-sensitive K+ channels located in vascular smooth muscle mediated relaxation of HIMA produced by resveratrol. P54 MATRIX METALLOPROTEINASE-9 (MMP-9), ITS TISSUE INHIBITOR TIMP-1 AND NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS NEW ATHEROSCLEROSIS MARKERS IN CHRONICALLY DIALYZED PATIENTS K. Musial, D. Zwolinska. Department of Pediatric Nephrology, Wroclaw Medical University, Wroclaw, Poland Background: Patients on chronic dialysis are prone to cardiovascular complications, being the first cause of morbidity and mortality. The MMP/TIMP proteolytic system may play an essential role in atherosclerosis, but the data concerning such influence in dialyzed patients are scarce. The aim of study was to assess concentrations of MMP-9 (gelatinase B) with anti-atherogenic activity, its specific inhibitor TIMP-1 and NGAL, preventing MMP-9 degradation by forming a dimer, in children and young adults on automated peritoneal dialysis (APD) and on hemodialysis (HD). Material and Methods: 22 children on APD, 17 patients on HD and 23 controls were examined. Serum concentrations of MMP-9, TIMP-1 and NGAL were assessed by ELISA. Serum CHOL, HDL-CHOL, LDL-CHOL, TGL and hsCRP were also evaluated. Results: Median values of MMP-9, TIMP-1, NGAL and MMP-9/NGAL ratio were significantly elevated in all dialyzed children vs. controls and were higher in HD than in APD. TIMP-1 values in HD exceeded 3 times those in APD. Consequently, the MMP-9/TIMP-1 ratio, although increased in APD (p < 0.00001) and HD (p < 0.01), was higher in APD than in HD (p < 0.00001). MMP-9 correlated with TGL in HD, TIMP-1 − with HDL-CHOL in HD and with hsCRP in APD. NGAL correlated with CHOL, HDL-CHOL and hsCRP in APD. Conclusions: Our results suggest the dysfunction of MMP/TIMP system in children on dialysis, with APD being less atherogenic than HD. Correlations with lipid profile and hsCRP may suggest the role of MMP-9, TIMP-1 and NGAL as new markers of atherosclerosis in the examined population. P55 THE TREATMENT OF COLESTERYL STORAGE DISEASE (CESD) BY EZETIMIBE MONOTHERAPY F. Abello1 , O. Guardamagna1 , V. Baracco1 , R. Bonardi2 . 1 Department of Pediatrics, 2 Department of Gastroenterology, University of Turin, Turin, Italy Objective: CESD is a rare lysosomal disorder affecting intrahepatic colesterol hydrolysis lacking a specific treatment. Ezetimibe, a cholesterol absorption inhibitor, should represent an option never delivered as monotherapy. Methods: A 15 yrs old male patient affected by CESD, diagnosed on the basis of liver steato-fibrosis and LIPA gene mutation, was treated with 10 mg/die for 2 yrs. Biochemical parameters were checked at basal time, 6 months, 1, 2 yrs since starting therapy. Liver enzymes, lipid profile were tested by standard methods. Inflammatory markers of lipid peroxidation interleukins 1beta (IL1b) and 6 (IL6) were evaluated using western blot analyses. Tranforming growth factor-beta1 (Tgf-beta1), choosen as hepatic fibrosis parameter was evaluated by elisa kit. The serum protein adducts Malonaldehyde (MDA) and 4-hydroxynonenal (HNE) were analyzed to test the oxidative damage. Liver elastograpy employed to test liver fibrosis. Results: Liver enzymes normalized by 6 months of therapy; total cholesterol and LDL-C decreased by 30% and 25% respectively at the same time. IL1b and IL6 decreased after one year of treatment. As well the oxidative markers malonaldehyde (MDA) and 4-hydroxynonenal (HNE) resulted 4.3±0.3 and 6.9±0.7 AFU/mg protein in basal condition and 3.8±0.5 and 5.1±0.5 AFU/mgprotein after 1 yr treatment, so showing a normal value. Tgfbeta1 did not change in agreement with unchanged elastografic fibrosis. Conclusion: Emphasis for CESD will lead to the disorder being recognized and correctly treated. Present results underline the well tolerated successful outcome reached by ezetimibe monotherapy in reducing lipoprotein levels, normalizing transaminases, cytokines and oxidative stress parameters. P56 INFLUENCE OF PHYSICAL TRAININGS ON BLOOD OXYGEN TRANSPORT INDICES AND ENDOTHELIAL FUNCTION IN PATIENTS WITH STABLE ANGINA L. Yankovskaya. Grodno State Medical University, Grodno, Belarus The aim of our study was to assess the efficiency of the medicinal treatment and bicycle trainings (BT) in patients with stable angina class II as for the indices of blood oxygen transport (BOT) and endothelial function. Group A included 16 patients which were treated with medicines. Group B included 10 patients which were treated with the same medicines plus BT for 14 days. BOT indices (pO2, pCO2, pH, Hb, metHb) were measured using microgas analyzer. The hemoglobin-oxygen affinity was determined according to the p50 index. Endothelium dependent vasodilatation (EDV) was measured by plethysmography. Plasma nitrite/nitrate level (NOx) was determined using Griess method.
Poster Presentations
Results: Maximally tolerated load increased only in group B by 27.8% (p < 0.05). The number of metabolic units also increased and was 7.80±0.47, which indicated improved assimilation of oxygen by tissues. “Double product”, indirectly characterizing assimilation of oxygen by myocardium, increased by 12.3% (p < 0.05) in group B and did not change in group A. Indices of BOT did not change, p50 increased in group A after treatment. In group B pO2 after treatment was 13.4% (p < 0.05) higher than in group A. pH increased to 7.334±0.009 units, p50 increased by 3.1% (p < 0.05). In group A EDV became 14.04±1.23% (p < 0.001). In group B EDV became 17.70±1.73% (p < 0.001) and was 26% higher, than in group A. NOx increased (p < 0.05) only in group B and was 21.81±1.09 mmol/l. Conclusion: BT improves more effectively oxygen supply of tissues and endothelial function as compared to medicinal treatment alone in patients with stable angina. P57 LIPO-RETRO-D-PEPTIDES: NEXT GENERATION OF THE HIGHMOST SELECTIVE THROMBIN INHIBITORS A. Poyarkov, S. Poyarkova. Protein Chemistry Department, Institute of Bioorganic Chemistry and Petrochemistry of the Ukrainian National Academy of Sciences, Kyiv, Ukraine The research is devoted to the investigation of structure–activity relationship (SAR) of novel inhibitors with a main target of the blood coagulation system enzyme-thrombin. Chemical modification of the main retro-D-peptide sequence − D-Arg-D-Pheby different aromatic, heterocyclic and aliphatic moieties led to discovery of lipo-retro-D-peptides − highmost selective thrombin inhibitors. Modification of the retro-D-peptide sequence − D-Arg-D-Phe- by fatty acids residues provided compounds which inhibit thrombin in the range of Ki from 2 to 0.1 mM and with selectivity of 200–6000 against trypsin. It has been proved that the well-known surfactant LAE (Na-Lauroyl arginine ethyl ester) is a competitive reversible thrombin inhibitor. It has been shown that LAE inhibits thrombin activity almost 20 times stronger than trypsin (Ki = 18.9 mM). At the same time LAE is hydrolyzed by thrombin at pH 8.5 (kcat = 3.6 c-1) and trypsin (kcat = 56 c-1) at the same pH. The LAE ability to activate plasmin at the same range of thrombin inhibition concentration deserves special attention. These findings establish an important role of fatty moiety in structure of inhibitors in preferential selective binding and inhibition of thrombin active side. Features of ion formation under the influence of laser emission under the conditions of MALDI-TOF mass spectrometry in the glycosylated protein thrombin and the related proteases trypsin and chymotrypsin were studied for the first time. In addition, the attempt to investigate features of thrombin-inhibitor interactions with MALDI TOF MS was made. P58 DETERMINATION OF THE PROOXIDANT–ANTIOXIDANT BALANCE IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY AND IN RENAL TRANSPLANT PATIENTS V. Markovic, T. Gojkovic, M. Kostic. University of Belgrade, Belgrade, Serbia Introduction: Several studies results indicate that oxidative stress might contribute to renal disease development. The aim of study: Determination of prooxidant–antioxidant balance (PAB) in patients with chronic renal insufficiency (HRI) and in renal transplant patients in purpose of identifying oxidative stress as risk factor in renal disease development. Methods and Material: Thirty-eight patients (12 patients with HRI and 26 renal transplant patients) and fifty healthy volunteers were chosen for this study. PAB, as indicator of oxidative stress state, was determined in plasma using spectrophotometric method. The absorbance of coloured compound, that is a product of reaction between 3,3 ,5,5 -tetramethylbenzidine and hydrogenperoxide, was read at 450nm. The results are expressed in HKU. Results: The results of this study indicate significant decreasing in antioxidative parameter values (enzyme SOD and SH-groups) of renal patients in comparison to control group, while the control group stated higher activity of antioxidative enzyme PON1. Increased values of SH-groups and decreased level of O−2 in patients with HBI indicate better antioxidative state in comparison to renal transplant patients. Significant increase of the PAB value was observed in renal patients in comparison to control group, but there was no significant difference betwen the two groups of patiens. In control group, positive corelation was found between PAB and leucocytes and negative corelation with enzym paraoxonase. Positive corelation between PAB and DZO in patients group probably represents a compensatory organism response. Conclusion: Measuring PAB might be useful for evaluation of oxidative stress state in patients with renal function failure.