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PubMed | Institute for Cardiovascular Diseases
Type: Journal Article | Journal: Clinical and experimental pharmacology & physiology | Year: 2016

Recent in vitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with proportion of sdLDL particles 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = -0.254, P = 0.034) and total cholesterol (r = -0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R(2) = 0.258; adjR(2) = 0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype.

Radak D.J.,University of Belgrade | Vlajinac H.D.,University of Belgrade | Marinkovic J.M.,University of Belgrade | Maksimovic M.Z.,University of Belgrade | Maksimovic Z.V.,Institute for Cardiovascular Diseases
Journal of Vascular Surgery | Year: 2013

Background: This was a psychometric validation of the short Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) as quality of life (QOL) instrument for chronic venous disease (CVD) patients. Methods: Patients aged >18 years who had CVD in CEAP C stages C0s to C6 were included in the study. Diagnosis was made by general practitioners according to CVD symptoms and visual examination of the lower extremities. QOL was assessed with the self-administrated CIVIQ-14. The reliability, construct, and convergent validity of the CIVIQ-14 was estimated as well as QOL of CVD patients according to CEAP C stages. Results: The study comprised 2260 subjects who fully completed the CIVIQ-14. CIVIQ-14 had a high level of reliability, construct, and convergent validity, but the structure of its three dimensions (pain [P], physical [PHY], and psychological [PSY]) was suboptimal. After adjustment for age, body mass index, and number of CVD symptoms, CIVIQ -14 global, P, PHY, and PSY scores showed significant progressive reduction of QOL from CEAP class C0s to C6. These differences were present in both sexes. The progressive impairment of the QOL involved primarily the pain and the physical items. For all CEAP C classes, the P and PHY scores were lower than the PSY scores. Global scores for men and women were: 76.7 and 73.9 for C 0s; 75.5 and 70.6 for C1; 67.8 and 64.5 for C2; 68.3 and 61.6 for C3; 60.7 and 54.6 for C4; 49.5 and 50.2 for C5; and 41.3 and 46.7 for C6. Conclusions: CVD in the lower extremities has a substantial effect on both physical and psychologic aspects of QOL, the physical aspects of QOL (P and PHY items) being more important. CIVIQ-14 is valuable in assessing QOL in CVD patients. Further investigations are necessary to confirm the stability of its two dimensions. © 2013 Society for Vascular Surgery.© 2013 by the Society for Vascular Surgery.

Djokovic A.,University of Belgrade | Stojanovich Lj.,University of Belgrade | Stanisavljevic N.,University of Belgrade | Bisenic V.,University of Belgrade | And 3 more authors.
Rheumatology International | Year: 2014

Patients with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. The aim of our study was to evaluate the importance of secondary antiphospholipid presence (SAPS) in light of carotid artery intima-media thickness (CIMT) changes in SLE patients. Our study included 120 patients with SLE (46.02 ± 13.16 years), 108 women and 12 men divided into two groups: 58 patients with SAPS and 62 SLE patients without SAPS taken as a control group. All patients underwent assessment of CIMT of right and left common carotid artery (CCA) and left and right internal carotid artery (ICA) by Doppler ultrasonography. In SAPS group, 48.3 % patients had significant changes of carotid arteries comparing to 16.1 % patients in control group (p = 0.008). Average CIMT values in left and right CCA and right ICA were significantly higher in SAPS group. No significant relationship between antiphospholipid antibody type and CIMT changes was established. Multivariate regression analysis revealed SAPS as a significant predictor of CIMT changes in SLE patients (p = 0.025). Presence of SAPS in SLE patients is associated with significant CIMT changes. Additional autoimmune burden leads to a need for a more aggressive education and prevention considering standard risk factors in this group of patients. © 2013 Springer-Verlag Berlin Heidelberg.

Djukanovic N.,Institute for Cardiovascular Diseases | Todorovic Z.,University of Belgrade | Obradovic S.,Military Medical Academy | Zamaklar-Trifunovic D.,Institute for Cardiovascular Diseases | And 4 more authors.
Journal of Pharmacological Sciences | Year: 2011

We aimed to examine the rate of thrombotic events after discontinuation of one year clopidogrel therapy in patients with implanted coronary stent, and to determine platelet aggregability by multiple electrode analyzer after cessation of clopidogrel. This prospective, multicenter study enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel one year after the stent placement. Platelet aggregation was measured using 3 agonists [adenosine diphosphate with PGE 1 (ADPHS), arachidonic-acid (ASPI), and thrombin receptor activating peptide (TRAP)] on the day of cessation of clopidogrel and at 10, 45, and 90 days after clopidogrel was stopped. Two thrombotic events were registered during the 6-months follow up (one ischemic stroke and one myocardial infarction; incidence of 1%). The mean values of ADP + PGE 1- and ASPI-induced aggregation 10 - 90 days after the cessation of clopidogrel were significantly higher than values obtained before the termination of the drug (P < 0.001, all). Cessation of clopidogrel did not influence the TRAP-induced aggregation, which reached the plateau in all measurements. In conclusion, the incidence of thrombotic events after the cessation of one-year clopidogrel treatment might be lower than expected in patients with implanted coronary stent. © The Japanese Pharmacological Society.

Djukanovic N.,High Medical School Milutin Milankovic | Todorovic Z.,University of Belgrade | Obradovic S.,Military Medical Academy | Njegomirovic S.,Alura Med D.o.o. | And 3 more authors.
Journal of Clinical Pharmacy and Therapeutics | Year: 2014

What is known and objective Premature discontinuation of clopidogrel in patients undergoing percutaneous coronary intervention is a significant risk factor for thrombotic adverse outcomes. However, recent studies indicate that even discontinuation of long-term use of clopidogrel may be associated with multiple adverse outcomes, that is, rebound phenomenon whose mechanism is not definitely clear. The aim of the study was to examine the effect of clopidogrel withdrawal in those on combined aspirin and clopidogrel therapy. Methods This prospective, multicenter study enrolled 200 patients who underwent coronary stent implantation and were on dual antiplatelet therapy (100 mg aspirin + 75 mg clopidogrel) 1 year after the stent placement. In all patients, we measured the platelet aggregation, by multiplate electrode aggregometry, using two agonists [adenosine diphosphate with PGE1 (ADPHS) and arachidonic acid (ASPI)] two times: on the day of cessation of clopidogrel and 90 days after clopidogrel was stopped. Results and discussion Following clopidogrel discontinuation, we registered an increase in ASPI values (P < 0·001), linear correlation between changes in ASPI and ADPHS values (P = 0·009) and significant difference in the values of ASPI first quartile of ADPHS compared with the other three (P < 0·001, P = 0·016, P < 0·001, I vs. II, I vs. III and I vs. IV quartile of ADPHS, respectively). What is new and conclusion Our findings show that cessation of clopidogrel causes loss of antiplatelet synergism with aspirin, leading to a weakening of the response to aspirin, which may be one explanation for the rebound after the clopidogrel cessation. Recent studies indicate that even discontinuation of long-term use of clopidogrel may be associated with multiple adverse outcomes, i.e. rebound phenomenon whose mechanism is not definitely clear. The aim of the study was to examine the effect of clopidogrel withdrawal in those on combined aspirin and clopidogrel therapy. Our findings show that cessation of clopidogrel causes loss of antiplatelet synergism with aspirin, leading to a weakening of the response to aspirin, which may be one explanation for the rebound after the clopidogrel cessation. © 2013 John Wiley & Sons Ltd.

Kotur-Stevuljevic J.,University of Belgrade | Peco-Antic A.,University of Belgrade | Spasic S.,University of Belgrade | Stefanovic A.,University of Belgrade | And 8 more authors.
Pediatric Nephrology | Year: 2013

Background: The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis. Methods: Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS). Results: Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS. Conclusions: Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase. © 2012 IPNA.

Feier H.,Institute for Cardiovascular Diseases | Ghez O.,Royal Brompton Hospital | Fraisse F.,La Timone Childrens Hospital | Kreitmann B.,La Timone Childrens Hospital
European Journal of Cardio-thoracic Surgery | Year: 2012

The simultaneous existence of double orifice right and left atrioventricular valves in the absence of ostium primum defects is rare and scarcely reported. We present the case of a 20-month old boy diagnosed with tetralogy of Fallot with pulmonary atresia who was found to have associated double-orifice mitral and tricuspid valves. © The Author 2011. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Kuschyk J.,University of Mannheim | Milasinovic G.,Institute for Cardiovascular Diseases | Kuhlkamp V.,Herz Zentrum Bodensee | Roberts P.R.,University of Southampton | And 6 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2014

Subcutaneous Defibrillation Introduction A purely subcutaneous implantable cardioverter defibrillator (ICD) requires higher energy but may be an effective alternative to transvenous ICDs to deliver lifesaving therapies. Objective To identify combinations of anteroposterior subcutaneous shock pathways and waveforms with defibrillation efficacy comparable to transvenous ICDs. Methods Defibrillation testing was performed in 141 patients temporarily implanted with an active can emulator and subcutaneous coil electrodes. The patients were subdivided into 5 groups within 2 study phases. In all groups, a posterior electrode was positioned with its tip close to the spine. In the first study phase, 2 different can locations were evaluated: (1) an inframammary pocket (IM-1-750), or (2) a conventional infraclavicular pocket (IC-1-750). In both cases, a 70 J biphasic shock was used (peak voltage 750 V; 270 μF capacitance). In the second phase, configuration IC-1-750 was enhanced by the addition of a second (parasternal) subcutaneous electrode (IC-2-750). Furthermore, the effects of a different 70 J shock waveform (1,000 V, 160 μF) were evaluated for configurations IM-1-750 and IC-2-750 (becoming IM-1-1000 and IC-2-1000). Results The proportion of patients satisfying a defibrillation safety margin test of 2 consecutive successes at ≤50 J was 74%, 11%, and 44%, respectively, for the IM-1-750, IC-1-750, and IC-2-750 configurations, and 93% and 86% for the IM-1-1000 and IC-2-1000 configurations. Conclusions Defibrillation efficacy comparable to that of a transvenous system was achieved with an anteroposterior subcutaneous ICD configuration, with 160 μF capacitance, 1,000 V, and 70 J output. An infraclavicular pocket location becomes feasible if a parasternal subcutaneous coil is added. © 2014 Wiley Periodicals, Inc.

Mandache E.,National Institute of Pathology | Gherghiceanu M.,National Institute of Pathology | Macarie C.,Institute for Cardiovascular Diseases | Kostin S.,Max Planck Institute for Heart and Lung Research | And 2 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

The human heart can be frequently affected by an organ-limited amyloidosis called isolated atrial amyloidosis (IAA). IAA is a frequent histopathological finding in patients with long-standing atrial fibrillation (AF). The aim of this paper was to investigate the ultrastructure of cardiomyocytes and telocytes in patients with AF and IAA. Human atrial biopsies were obtained from 37 patients undergoing cardiac surgery, 23 having AF (62%). Small fragments were harvested from the left and right atrial appendages and from the atrial sleeves of pulmonary veins and processed for electron microscopy (EM). Additional fragments were paraffin embedded for Congo-red staining. The EM examination certified that 17 patients had IAA and 82% of them had AF. EM showed that amyloid deposits, composed of characteristic 10-nm-thick filaments were strictly extra-cellular. Although, under light microscope some amyloid deposits seemed to be located within the cardiomyocyte cytoplasm, EM showed that these deposits are actually located in interstitial recesses. Moreover, EM revealed that telopodes, the long and slender processes of telocytes, usually surround the amyloid deposits limiting their spreading into the interstitium. Our results come to endorse the presumptive association of AF and IAA, and show the exclusive, extracellular localization of amyloid fibrils. The particular connection of telopodes with amyloid deposits suggests their involvement in isolated atrial amyloidosis and AF pathogenesis. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Wiesner C.,University of Hamburg | Faix J.,University of Hamburg | Himmel M.,University of Hamburg | Bentzien F.,Hannover Medical School | And 2 more authors.
Blood | Year: 2010

The matrix metalloproteinase (MMP) MT1-MMP plays pivotal roles in leukocyte physiology such as monocyte diapedesis, dendritic cell migration, and T-cell homing. MT1-MMP is a surface-anchored "master switch" proteinase that cleaves a variety of substrates including extracellular matrix components, matrix receptors, and also other MMPs. However, little is known about the mechanisms enabling intracellular trafficking and exposure of MT1-MMP on the cell surface. We now show that, in primary human macrophages, MT1-MMP-positive vesicles travel bidirectionally along microtubules, in a process regulated by KIF5B and KIF3A/KIF3B kinesins. SiRNA-induced knockdown revealed that transport by KIF5B and KIF3A/KIF3B is crucial for delivery of MT1-MMP to the cell surface and also for surface-associated functions of MT1-MMP, such as shedding of the matrix receptors CD44 and syndecan-1 or degradation of extracellular matrix at podosomes. These data show that kinesin-mediated intracellular transport of MT1-MMP is a pivotal process that allows macrophages to dynamically modify their pericellular environment. These data also identify specific kinesins as potential targets for the early manipulation of MT1-MMP activity in tissues. © 2010 by The American Society of Hematology.

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