Biomedical subjects

Johann Wojta

Publications and source records attributed to Johann Wojta.

At least 19 recordsLinked to original sources

PubMed2006

Oxidized phospholipids stimulate angiogenesis via autocrine mechanisms, implicating a novel role for lipid oxidation in the evolution of atherosclerotic lesions.

Angiogenesis is a common feature observed in advanced atherosclerotic lesions. We hypothesized that oxidized phospholipids (OxPLs), which accumulate in atherosclerotic vessels can stimulate angiogenesis. We found that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) stimulated the formation of sprouts from endothelial cell spheroids and promoted growth of capillaries into Matrigel plugs in mice. OxPLs stimulated expression of vascular endothelial growth factor (VEGF) in vivo and in several normal and tumor cell types in vitro. In addition, OxPAPC upregulated cyclooxygenase (COX)-2 and interleukin (IL)-8. COX-2 inhibitors, as well as blocking antibodies to IL-8 suppressed activation of sprouting by OxPAPC. We conclude that OxPAPC stimulates angiogenesis via autocrine mechanisms involving VEGF, IL-8, and COX-2-generated prostanoids. Our data suggest that accumulation of OxPLs may contribute to increased growth of blood capillaries in advanced lesions, thus leading to progression and destabilization of atherosclerotic plaques.

ADAM Proteins↗

PubMed2006

Monocyte chemoattractant protein (MCP-1) is expressed in human cardiac cells and is differentially regulated by inflammatory mediators and hypoxia.

The chemokine MCP-1 is thought to play a key role - among many other pathophysiological processes - in myocardial infarction. MCP-1 is not only a key attractant for monocytes and macrophages and as such responsible for inflammation but might also be directly involved in the modulation of repair processes in the heart. We show that cultured human cardiac cells express MCP-1 and that its expression is upregulated by inflammatory cytokines and downregulated by hypoxia. We hypothesize that inflammation but not hypoxia is the main trigger for monocyte recruitment in the human heart.

Cell Hypoxia↗

PubMed2006

Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction.

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.

Adult↗

PubMed2006

Hydroxymethylglutaryl-coenzyme A reductase inhibitors induce apoptosis in human cardiac myocytes in vitro.

Recent findings have implicated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins, an established class of drugs for the treatment of hypercholesterolemia, in tissue remodeling in the heart. Statins induce apoptosis in different cell culture systems including rat neonatal cardiomyocytes. We investigated possible effects of different statins in vitro in human adult cardiac myocytes on the expression of proteins thought to be involved in the regulation of apoptosis such as Mcl-1, an inhibitor of apoptosis, Bax, an inducer of apoptosis, as well as on cytoplasmic histone-associated-DNA-fragments. Human adult cardiac myocytes (HACM) were treated with different statins at concentrations from 0.01 to 5 microM for up to 96 h. Whereas the lipophilic statin simvastatin at a concentration of 5 microM downregulated Mcl-1 mRNA by 49%, the hydrophilic pravastatin had no effect. Bax mRNA levels were not affected by neither of the statins. Simvastatin but not pravastatin reduced Mcl-1 protein expression whereas Bax protein was not detectable in HACM as determined by Western blotting. Simvastatin, atorvastatin and fluvastatin induced an up to seven-fold increase in histone-associated-DNA-fragments whereas pravastatin did not. Simvastatin up regulated histone-associated-DNA-fragments dose-dependently, and mevalonate and geranylgeranyl pyrophosphate reversed this effect to control levels. Our results show that lipophilic statins can induce a pro-apoptotic state in human adult cardiac myocytes in vitro. We speculate that, similar to findings in animal models, statins might be involved in the attenuation of cardiac hypertrophy and remodeling in humans by modulating the balance between cell survival and apoptosis.

Adult↗

PubMed2006

Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo.

In addition to lipid lowering effects, statins appear to have pleiotropic immunomodulatory properties. As they particularly affect monocyte functions, we tested the influence of statin treatment on the monocyte activating toll-like receptors (TLR) 4 and 2 in response to lipopolysaccharides (LPS) in vivo. In this double-blind, placebo-controlled study, 20 healthy, male subjects were randomized to receive either simvastatin (80 mg/day) or placebo for 4 days before intravenous LPS administration (20 IU/kg). Simvastatin did not influence the increase in TLR transcripts after LPS administration measured in mRNA isolated from whole blood by quantitative RT-PCR. In contrast, the parallel upregulation of TLR4 and TLR2 on the surface of monocytes determined by flow cytometry was attenuated by more than half after LPS challenge (P<0.02). Suppressed TLR4 and TLR2 expression was associated with diminished circulating concentrations of tumor necrosis factor-alpha and monocyte chemoattractant protein-1. In conclusion, high-dose simvastatin pretreatment blunted TLR4 and TLR2 expression on monocytes in a human endotoxemia model on a posttranscriptional level. This suppressive effect of statins on key receptors of the innate immunity which was associated with a reduction of effector cytokines reveals a potential mechanism for their beneficial effects in sepsis and cardiovascular disease.

Adult↗

PubMed2006

Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours.

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported. The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating. Circulating pre- and post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n = 12; and AST-Bare, n = 7) died mean 6.3 +/- 2.9 h after stent implantation from AST. The remaining 122 control (C) pigs (groups C-DES, n = 76, and C-Bare, n = 46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 +/- 1.12 and 11.6 +/- 0.68 vs. 8.85 +/- 0.78 and 9.04 +/- 0.81 fL; p < 0.001), similarly to TF-ag (189.1 +/- 87.5 and 127 +/- 34.9 vs. 42.5 +/- 24.6 and 35.3 +/- 37.6 pg/ml; p < 0.001, respectively), Tfact (3.23 +/- 0.95 and 2.73 +/- 1.68 vs. 1.43 +/- 1.12 and 1.61 +/- 1.31 pM; p < 0.01, respectively) and PAI-1 (99.1 +/- 15.8 and 99 +/- 14.7 vs.53.4 +/- 40.2 and 46.9 +/- 42.4 ng/ml;p < 0.01, respectively). Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p = 0.016) and MPV (p = 0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.

Angiography↗

PubMed2006

The estrogen metabolite 17beta-dihydroequilenin counteracts interleukin-1alpha induced expression of inflammatory mediators in human endothelial cells in vitro via NF-kappaB pathway.

In most studies showing cardio- and vasculoprotective effects of estrogens, 17beta-estradiol was used and little information on possible effects of different estrogen metabolites is yet available. We investigated whether particular estrogen metabolites are effective in counteracting inflammatory activation of human endothelium. Human endothelial cells were incubated with 17alpha-dihydroequilenin, 17beta-dihydroequilenin, delta-8,9-dehydroestrone, estrone and 17beta-estradiol and stimulated with interleukin (IL)-1alpha. The expression of IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) was determined. 17beta-dihydroequilenin and 17beta-estradiol at a concentration of 1 microM reduced IL-1alpha-induced up regulation of IL-6, IL-8 and MCP-1 close to control levels. When both compounds were used in combination an additive effect was observed. 17alpha-dihydroequilenin and delta-8,9-dehydroestrone showed a similar anti-inflammatory effect only when used at 10 microM whereas estrone had no effect. The effect of 17beta-dihydroequilenin on IL-1alpha-induced production of IL-6, IL-8 and MCP-1 was reversed by the estrogen receptor antagonist ICI 182,780. 17beta-dihydroequilenin also inhibited IL-1alpha-induced translocation of p50 and p65 to the nucleus of the cells. We have identified the estrogen metabolite 17beta-dihydroequilenin, as an inhibitor of inflammatory activation of human endothelial cells. Characterization of specific estrogens--as shown in our study--could provide the basis for tailored therapies, which might be able to achieve vasoprotection without adverse side effects.

Anti-Inflammatory Agents↗

PubMed2005

Endurance training reduces circulating inflammatory markers in persons at risk of coronary events: impact on plaque stabilization?

Inflammatory pathways are involved in destabilization of atherosclerotic plaques. We assessed the hypothesis that endurance training decreases circulating concentrations of inflammatory markers in persons with coronary artery disease (CAD) and cardiovascular risk factors (CVRFs). Thirty-two subjects with CAD and/or CVRFs joined a 12-week supervised endurance training. We found a significant decrease of the chemokines interleukin (IL)-8 (pre: 3.9+/-0.6, change: -1.2+/-0.4 pg/ml, -21%, p=0.002) and monocyte chemoattractant protein-1 (pre: 213+/-9, change: -20.4+/-8.2 pg/ml, -5%, p=0.03). Diabetes mellitus (DM) significantly influenced changes of IL-8 (p=0.002). IL-8 substantially dropped by 39% in diabetics. Moreover, matrix metalloproteinase-9 (MMP-9) highly significantly decreased in response to training (pre: 750+/-98, change: -278+/-77 ng/ml, -18%, p=0.005). Exercise-induced changes of MMP-9 were influenced by concomitant use of statins (p=0.038). We observed a particularly strong MMP-9 reduction of 44% in patients treated with statins. Acute phase reactants IL-6 (pre: 1.7+/-0.3, change: +0.25+/-0.7 pg/ml, +4%, p=0.58) and high sensitivity C-reactive protein (pre: 2.1+/-0.5, change: -0.25+/-0.4 mg/l, -9%, p=0.54) did not change in response to training. In conclusion, endurance training decreased circulating chemokines and MMP-9, which may in part explain its beneficial effect on coronary risk. Patients with DM or treated with statins because of hypercholesterolemia may particularly take advantage.

Chemokine CCL2↗

PubMed2005

Clinical restenosis after coronary stent implantation is associated with the heme oxygenase-1 gene promoter polymorphism and the heme oxygenase-1 +99G/C variant.

BACKGROUND: Vascular remodeling after percutaneous coronary stent implantation frequently leads to restenosis. Heme oxygenase 1 (HO-1) is involved in the generation of the endogenous antioxidant bilirubin and carbon monoxide, both of which exert antiinflammatory and antiproliferative effects. The aim of the present study was to evaluate the influence of genetic risk factors combined with the conventional risk factors on the development of coronary restenosis after percutaneous coronary intervention (PCI) with stent implantation. METHODS: The HO-1 gene GT dinucleotide repeat promoter polymorphism and HO-1 +99G/C variant were evaluated in 199 patients with coronary artery disease after coronary stent implantation and control angiography at 6 months after the intervention. Coronary restenosis was confirmed by quantitative angiography. RESULTS: Carriers of the long allele of the HO-1 gene promoter (>29 repeats) had a significantly higher risk of developing restenosis after PCI than noncarriers [odds ratio (OR)=1.9; 95% confidence interval (95% CI), 1.0-3.4; P=0.04]. Interestingly, the allele longer than 29 repeats conferred a significantly higher risk of developing restenosis (OR=3.4; 95% CI, 1.2-9.1; P=0.017) in nonsmokers than in smokers (OR=2.0; 95% CI, 0.7-5.2; P=0.18). CONCLUSIONS: The long allele of the HO-1 gene promoter (>29 repeats) polymorphism, which leads to low HO-1 inducibility, may represent an independent prognostic marker for restenosis after PCI and stent implantation. The effect of the >29 repeat allele is attenuated in smokers, who have chronic exogenous CO exposure.

Aged↗

PubMed2005

Complement component C5a predicts future cardiovascular events in patients with advanced atherosclerosis.

AIMS: Complement activation occurs in atherosclerotic lesions, and particularly complement component C5a exerts potent chemotactic and proinflammatory effects. However, it is yet unknown, whether plasma levels of C5a may predict cardiovascular risk. The aim of this study was to examine whether plasma levels of the complement component C5a may predict cardiovascular risk in patients with advanced atherosclerosis. METHODS AND RESULTS: We studied 173 patients with symptomatic peripheral artery disease (median age 72, 82 male). Cardiovascular risk profile, levels of the complement factor C5a, and other non-specific inflammatory parameters [high sensitivity C-reactive protein, serum amyloid A (SAA), and fibrinogen] were obtained at baseline, and patients were followed for median 22 months [interquartile range (IQR) 13-27] for the occurrence of major adverse cardiovascular events (MACE: myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 65 MACE in 49 patients (28%). Cumulative event rates (95% confidence interval (CI)) within quartiles of C5a at 24 months were 16 (5-27), 26 (13-39), 36 (21-51), and 37% (23-51), respectively (P=0.0077). Adjusted hazard ratios for the occurrence of a first MACE according to increasing quartiles of C5a were 1.81, 2.23, and 2.66, respectively, as compared to the lowest quartile (P=0.038), irrespective of the level of other inflammatory parameters. CONCLUSION: Complement activation, indicated by the elevation of C5a, seems to be associated with increased cardiovascular risk in patients with advanced atherosclerosis. Clinically, determination of C5a may add to the predictive value of other non-specific inflammatory parameters.

Aged↗

PubMed2005

Simvastatin blunts endotoxin-induced tissue factor in vivo.

BACKGROUND: Beyond lipid lowering, various antiinflammatory properties have been ascribed to statins. Moreover, in vitro studies have suggested the presence of anticoagulant effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, as lipopolysaccharide (LPS)-induced monocyte tissue factor (TF) was suppressed. In this study, we examined the role of statins in experimental endotoxemia on inflammatory and procoagulant responses in vivo. METHODS AND RESULTS: In this double-blind, placebo-controlled, parallel-group study, 20 healthy, male subjects were randomized to receive either simvastatin (80 mg/d) or placebo for 4 days before intravenous administration of LPS (20 IU/kg IV). Plasma high-sensitive C-reactive protein (hsCRP), monocyte chemoattractant protein (MCP-1), sCD40L, sCD40, and prothrombin fragment F1+2 (F1.2) were determined by ELISAs at baseline and at 4 and 8 hours after LPS administration. Monocyte TF expression and monocyte-platelet aggregates were measured by whole-blood flow cytometry over the same time course. The increases in hsCRP and MCP-1, both known inducers of TF, were significantly suppressed by statin treatment after LPS challenge. Statin premedication blunted the increase of monocyte TF expression in response to LPS. In parallel, endotoxin-induced formation of F1.2 was significantly reduced by simvastatin after 4 and 8 hours. LPS infusion affected neither the formation and activation of monocyte-platelet aggregates nor plasma levels of sCD40 and sCD40L. CONCLUSIONS: Simvastatin suppresses the inflammatory response to endotoxin and blunts monocyte TF expression but does not affect platelet activation.

Adult↗

PubMed2005

New cut-off values of cardiac markers for risk stratification of angina pectoris.

BACKGROUND: The aim of this present prospective study was to investigate the accuracy of cardiac markers for the prediction of subsequent cardiac events (cardiac death, acute myocardial infarction and recurrent ischemia requiring coronary revascularization). METHODS: Fibrinogen, cardiac troponin T, troponin I, creatine phosphokinase myocardial fraction, C-reactive protein and myoglobin at baseline and after 6 h were measured on 154 patients (109 male, 63+/-11 years) with chest pain. Receiver operator characteristic analyses were performed to determine cut-off points of cardiac markers in prediction of adverse events. RESULTS: The following cut-off values for prediction of cardiac events were calculated: troponin I at baseline 0.3 ng/ml (predictive accuracy=0.870), troponin I at 6 h 0.50 ng/ml (p.a.=0.909); troponin T at baseline 0.05 ng/ml (p.a.=0.643), troponin T at 6 h 0.05 ng/ml (p.a.=0.612), creatine phosphokinase myocardial fraction at baseline 2.0 ng/ml (p.a.=0.721), creatine phosphokinase myocardial fraction at 6 h 2.5 ng/ml (p.a.=0.734), myoglobin at baseline 23 ng/ml (p.a.=0.623), myoglobin at 6 h 26 ng/ml (p.a.=0.617), C-reactive protein at baseline 0.31 mg/dl (p.a.=0.662), C-reactive protein at 6 h 0.55 mg/dl (p.a.=0.682), and fibrinogen at baseline 360 mg/dl (p.a.=0.701). The combination of baseline troponin I with different parameters resulted in a higher sensitivity of up to 98%, with a similar predictive accuracy, but a lower specificity. Additive measurements of cardiac troponin I at 6 h to baseline cardiac troponin T and I proved to be the best combination for prediction of subsequent cardiac events. CONCLUSIONS: Changes in cut-off levels of cardiac markers and inflammatory parameters results in a high accuracy of risk stratification in patients with chest pains. Combination of these measurements might further help in the identification of patients who would benefit from early coronary revascularization.

Aged↗

PubMed2005

Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease.

OBJECTIVE: As regular physical exercise improves endothelial dysfunction and promotes cardiovascular health, we investigated the effect of training on angiogenesis by measuring the number of circulating endothelial progenitor cells (EPC), the level of EPC-mobilizing growth factors and tested vascular function by flow-mediated dilation (FMD) in patients with coronary artery disease (CAD) and cardiovascular risk factors (CVRF). In addition, degradation products of the NO pathway (NOx) were determined. METHODS AND RESULTS: Twenty patients with documented CAD and/or CVRF joined a 12-week supervised running training. Circulating EPCs--defined by the surface markers CD34, KDR and CD133--were measured at baseline and after exercise training by flow cytometry. We found a significant increase in circulating EPCs (2.9+/-0.4-fold increase; P < .0001), which was positively correlated with both, the change of FMD (r = .81, P < .001) and the increase of NOx synthesis (r = .83, P < .001). Plasma VEGF and erythropoietin did not change in response to exercise. However, we observed a positive correlation between the number of EPCs and erythropoietin at baseline (r = .70, P < .01) and after training (r = .73, P < .01). CONCLUSIONS: Regular exercise training augments the number of circulating EPCs in patients with CVRF and CAD and is associated with improved vascular function and NO synthesis.

Adult↗

PubMed2005

An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.

OBJECTIVES: The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system. BACKGROUND: Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation. METHODS: We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm. RESULTS: Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO. CONCLUSIONS: Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.

Aged↗

PubMed2005

[Direct and indirect antithrombins in acute coronary syndromes].

Unfractionated heparin (UFH) as well as low-molecular-weight heparins (LMWH), especially enoxaparin, are recommended by the current international guidelines for routine used in the conservative treatment of patients with acute coronary syndromes (ACS). UFH is still the recommended antithrombin as soon as percutaneous coronary interventions (PCI) are performed, although the results of different trials clearly have demonstrated the benefit of enoxaparin also in interventional cardiology. Bleeding complications along PCI procedures can be minimized by avoiding crossover from enoxaparin to UFH or vice versa and by reducing the dosage of indirect antithrombins, particularly of enoxaparin, in patients with chronic renal dysfunction and/or the elderly. Especially for those patient groups, bivalirudin offers already today an effective alternative. There is increasing expectation concerning the use of bivalirudin in patients undergoing PCI procedures but firm data exist at present only for low- and medium-risk patients with non ST-elevation ACS. Results of still ongoing trials (ACUITY, HORIZONS) will help to further confirm the role of bivalirudin in patients with high-risk acute coronary syndromes. For other direct antithrombins, e.g., fondaparinux (a pentasaccharide) or melagatran, comparably few data are available at present. Whether these agents will make their way into clinical use, future will tell.

Acute Disease↗

PubMed2005

The adaptive immune system and long-term outcome in patients with stable coronary disease. Predictive value of routine laboratory measurements.

Components of the adaptive immune system, in particular lymphocytes and immunoglobulin, play a major role in advanced atherosclerotic lesions. We sought to determine whether routine, measurements of the relative number of circulating lymphocytes (%L) and gamma-globulin (%G) reflecting immunoglobulin are related to event-free survival in patients with stable coronary artery disease (CAD). We prospectively studied the combined endpoint all-cause mortality, myocardial infarction and coronary revascularization procedures in 141 patients after successful percutaneous coronary intervention during a median follow-up time of 13.2 years. Using Cox regression, we found a significant influence of %L on event-free survival (P=0.007) with a relative risk of 2.21 comparing third to first tertile. Subjects with higher %G values likewise had a shorter event-free survival (P=0.008) with a relative risk of 1.67 comparing third to first tertile. The predictive value of %L and %G remained significant after adjustment for demographic data, cardiovascular risk factors, extent of CAD and other inflammatory markers. We conclude that the fraction of gamma-globulin and in particular the relative lymphocyte cell count may serve as readily available and reliable prognostic tools for the long-term outcome in patients with stable CAD.

Arteriosclerosis↗

PubMed2005

Opposite effects of CX3CR1 receptor polymorphisms V249I and T280M on the development of acute coronary syndrome. A possible implication of fractalkine in inflammatory activation.

Several lines of evidence suggest that the chemokine fractalkine (FKN) and its receptor CX3CR1 contribute to the accumulation of leukocytes in the atherosclerotic plaque. The M280 allele of the CX3CR1T280M polymorphism modulates leukocyte recruitment and is associated with lower prevalence of cardiovascular disease. The influence of V249I, another CX3CR1 polymorphism, is discussed controversially. We investigated the association of the alleles M280 and I249 of CX3CR1 with coronary artery disease (CAD) and with acute coronary syndrome (ACS). Additionally, we assessed their association with the soluble ligand FKN and inflammatory activation measured by high sensitivity C-reactive protein (hsCRP). The genotypes of the V249I and T280M polymorphisms were determined in 1152 patients with suspected CAD.720 (62.5%) individuals showed significant CAD with an ACS prevalence of 59.3%. Using multivariate regression, we found a harmful influence of I249 (adjusted OR=1.8, P<0.03) and a protective effect of M280 (adjusted OR=0.6, P<0.04) on the occurrence of ACS in patients with CAD. Correspondingly, patients with I249 but without M280 (17%) were at elevated risk of ACS (OR=1.6, P<0.04). During ACS these patients (carrying only I249) had significantly higher circulating concentrations of FKN and high sensitivity C-reactive protein (1.9- and 1.6-fold). We found no association of the I249 or the M280 allele with the occurrence of CAD. In conclusion, I249 and M280 have opposite effects on the occurrence of ACS. The presence of I249 not "balanced" by M280 confers an elevated risk of ACS. A FKN-mediated enhanced inflammatory activation might explain this increased risk.

Acute Disease↗

PubMed2005

Ultrasound thrombolysis.

Cardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, therefore, to make thrombolytic therapies more effective and safer. Ultrasound Thrombolysis is a technique which showed promising results under in vitro conditions and in animal studies. Now clinical trials have to prove if it is also feasible for clinical application. This report gives an overview on different technical approaches and their current performances in the clinical setting. All original articles are chronologically ordered in tables providing detailed information on each study concerning experimental design, acoustical parameters and thrombolysis outcome.

Acoustics↗