Search

The sports medicine performance diagnostics include investigative procedures that supply information on the performance capacity and stamina of an athlete. This creates a foundation for a personalised training plan and enables optimised control of the training process.The study population consisted of 24 male Nordic combined athletes from the national German squad. They were monitored using sports medicine over a period of five winter seasons. The test speeds on the treadmill in m/s are determined at lactate values of 2, 3 and 4 mmol/l in the peripheral blood values to calculate the lactate curve.The higher the test performance expressed as a percentage, the more likely it was that a top position could be achieved. The individual anaerobic threshold and the maximal oxygen uptake increased significantly with an increase in test performance expressed as a percentage. The older the athlete, the better they performed in the overall world cup. When age increased, the test speed [m/s] at lactate values of 2, 3 and 4 mmol/l also increased, along with the test performance expressed as a percentage, the maximal oxygen uptake and the individual anaerobic threshold. A higher BMI proved advantageous in terms of placement in the individual competitions.In this study the test speed at a lactate concentration of 4 mmol/l can be recommended as a robuster, more independent from mathematical models and physiologically more valid parameter for performance diagnostics in professional athletes.

In the last few years, the muscular system has gained attention due to the discovery of the muscle-secretome and its high potency for retaining or regaining health. These cytokines, described as myokines, released by the working muscle, are involved in anti-inflammatory, metabolic and immunological processes. These are able to influence human health in a positive way and are a target of research in metabolic diseases, cancer, neurological diseases, and other non-communicable diseases. Therefore, different types of exercise training were investigated in the last few years to find associations between exercise, myokines and their effects on human health. Particularly, resistance training turned out to be a powerful stimulus to enhance myokine release. As there are different types of resistance training, different myokines are stimulated, depending on the mode of training. This narrative review gives an overview about resistance training and how it can be utilized to stimulate myokine production in order to gain a certain health effect. Finally, the question of why resistance training is an important key regulator in human health will be discussed.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4–8%) as well as in low-risk patients (STS-Score

ZusammenfassungDie EU-Verordnung 1178/2011 fordert in speziellen Fällen eine erweiterte kardiovaskuläre Beurteilung, der Umfang ist jedoch nicht spezifiziert. Neben Ergometrie, Echokardiografie und Doppler der Halsgefäße werden vom Luftfahrtbundesamt zahlreiche Laborparameter gefordert. In den Leitlinien zum Management der stabilen koronaren Herzkrankheit ist die Ergometrie weitgehend obsolet. Stress-Echokardiografie und Stress- MRT bieten eine bessere diagnostische und prognostische Beurteilung. Die Spiroergometrie kombiniert die Ergometrie mit einer Messung respiratorischer Parameter. Hierüber kann das Herzzeitvolumen abgeschätzt und ischämische Veränderungen detektiert werden. Die Wertigkeit in der Erkennung ischämischer Veränderungen entspricht der des Stress-MRT bei signifikant niedrigeren Kosten. Bei einer Spiroergometrie ohne Ischämiezeichen ist die negative prädiktive Wertigkeit sehr hoch. Wir empfehlen die Spiroergometerie deshalb als Ersatz teurer prognostischer Untersuchungen.

Aims: The diagnostic approach to idiopathic giant-cell myocarditis (IGCM) is based on identifying various patterns of inflammatory cell infiltration and multinucleated giant cells (GCs) in histologic sections taken from endomyocardial biopsies (EMBs). The sampling error for detecting focally located GCs by histopathology is high, however. The aim of this study was to demonstrate the feasibility of gene profiling as a new diagnostic method in clinical practice, namely in a large cohort of patients suffering from acute cardiac decompensation. Methods and Results: In this retrospective multicenter study, EMBs taken from n = 427 patients with clinically acute cardiac decompensation and suspected acute myocarditis were screened (mean age: 47.03 &plusmn, 15.69 years). In each patient, the EMBs were analyzed on the basis of histology, immunohistology, molecular virology, and gene-expression profiling. Out of the total of n = 427 patient samples examined, GCs could be detected in 26 cases (6.1%) by histology. An established myocardial gene profile consisting of 27 genes was revealed, this was narrowed down to a specified profile of five genes (CPT1, CCL20, CCR5, CCR6, TLR8) which serve to identify histologically proven IGCM with high specificity in 25 of the 26 patients (96.2%). Once this newly established profiling approach was applied to the remaining patient samples, an additional n = 31 patients (7.3%) could be identified as having IGCM without any histologic proof of myocardial GCs. In a subgroup analysis, patients diagnosed with IGCM using this gene profiling respond in a similar fashion to immunosuppressive therapy as patients diagnosed with IGCM by conventional histology alone. Conclusions: Myocardial gene-expression profiling is a promising new method in clinical practice, one which can predict IGCM even in the absence of any direct histologic proof of GCs in EMB sections. Gene profiling is of great clinical relevance in terms of a) overcoming the sampling error associated with purely histologic examinations and b) monitoring the effectiveness of therapy.

Objectives Although regular physical exercise clearly reduces cardiovascular morbidity risk, long-term endurance sports practice has been recognized as a risk factor for atrial fibrillation (AF). However, the mechanisms how endurance sports can lead to AF are not yet clear. The aim of our present study was to investigate the influence of long-term endurance training on vagal tone, atrial size, and inflammatory profile in professional elite soccer players. Methods A total of 25 professional major league soccer players (mean age 24 ± 4 years) and 20 sedentary controls (mean age 26 ± 3 years) were included in the study and consecutively examined. All subjects underwent a sports cardiology check-up with physical examination, electrocardiography, echocardiography, exercise testing on a bicycle ergometer, and laboratory analysis [standard laboratory and cytokine profile: interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-8, IL-10]. Results Athletes were divided into two groups according to presence or absence of an early repolarization (ER) pattern, defined as a ST-segment elevation at the J-point (STE) ≥0.1 mm in 2 leads. Athletes with an ER pattern showed significantly lower heart rate and an increased E/e′ ratio compared to athletes without an ER pattern. STE significantly correlated with E/e′ ratio as well as with left atrial (LA) volume. The pro-inflammatory cytokines IL-6, IL-8, TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in all soccer players. However, athletes with an ER pattern had significantly higher IL-6 plasma levels than athletes without ER pattern. Furthermore, athletes with “high” level IL-6 had significantly larger LA volumes than players with “low” level IL-6. Conclusions Athletes with an ER pattern had significantly higher E/e′ ratios, reflecting higher atrial filling pressures, higher LA volume, and higher IL-6 plasma levels. All these factors may contribute to atrial remodeling over time and thus increase the risk of AF in long-term endurance sports.

Customer referral programs (CRPs) are widely applied as an effective means to stimulate word-of-mouth. While previous research mainly focuses on CRPs’ impact of acquiring new customers, this study introduces referral programs as a strategic brand management tool. In doing so, this article emphasizes what has been largely neglected by scholars: A “recommenders-perspective.” Guided by two competing theoretical perspectives, this article proposes that the perceived congruity between a reward and the recommended brand is an essential driver of referral program performance outcomes. The results show that rewards that conform to the image of the recommended brand yield more favorable reward attractiveness perceptions. Furthermore, the authors show that reward attractiveness perceptions inevitably affect the brand customers are asked to recommend in exchange for receiving this reward. The research reported here extends the literature on judgmental evaluations resulting from schema-based processing and provides novel insights into the design of CRPs.

Atherosclerosis is associated with chronic inflammatory responses of the arterial blood vessels. The previously observed protective effect of the MCS-18 substance against the initiation of atherosclerosis in a murine model was explained by its pronounced anti-inflammatory activity. Here, we investigated its impact on murine plaque progression in advanced atherosclerosis and on proatherogenic processes.ApoE-deficient mice were fed a high-fat diet for 12 weeks to induce atherosclerosis, followed by normal chow and intraperitoneal injections of either MCS-18 (500 μg, n = 10) or saline (n = 10) twice a week for another 12 weeks. Plaque size was reduced in MCS-18 treated mice compared to controls (p = 0.001), which was associated with a reduced size of the lipid core (p = 0.01). There was a decrease in apoptotic cells (p = 0.02), endothelial ICAM-1 expression (p0.001), and macrophage density (p = 0.01) in the MCS-18 group. In addition, human and murine dendritic cells (DCs) and human umbilical vein endothelial cells (HUVECs) were treated with MCS-18 (50-200 μg/ml) to analyze cell migration and adhesion under flow conditions. MCS-18 reduced human (p = 0.01) and murine (p = 0.006) DC migration. Furthermore, adhesion of MCS-18-treated DCs to a HUVEC monolayer was decreased (p0.001). Compared to controls, CD209 (p0.001) and CCR7 (p = 0.003) expression was decreased in MCS-18-treated DCs, while in HUVECs lower levels of ICAM-1 (p0.001) and of phosphorylated NF-κB-p65 (p = 0.002) were observed. Blocking of ICAM-1 reduced DC adhesion (p0.001).MCS-18 exhibits interesting therapeutic effects when applied in advanced murine atherosclerosis. Its antiatherogenic impact might be associated with a suppressed adhesion to the endothelium due to down-regulation of endothelial ICAM-1 expression.

Predictors of long-term outcome after ST-elevation myocardial infarction (STEMI) complicated by out-of-hospital cardiac arrest (OHCA) are incompletely understood, including the influence of successful coronary reperfusion.We analysed clinical and procedural data as well as 1-year outcome of 72 consecutive patients who underwent primary coronary intervention (PCI) after witnessed OHCA and STEMI and compared the results with 695 patients with STEMI and PCI, but without OHCA. Neurological recovery after OHCA was assessed using the Cerebral Performance Category (CPC) scale.PCI was successful in 83.3% after OHCA vs. 84.3% in the non-OHCA group (p=0.87). One-year mortality was 34.7% vs. 9.5% (p0.001). 58.3% of the OHCA-patients showed complete neurological recovery (CPC 1) or moderate neurological disability (CPC 2). Another 6.9% showed severe cerebral disability (CPC 3) or permanent vegetative status (CPC 4). Delay from collapse until start of Advanced Cardiopulmonary Life Support (ACLS) was shorter for survivors with CPC status ≤2 (median 1 min, range 0-11 min) compared to non-survivors or survivors with CPC status2 (median 8 min, range 0-13 min), p0.0001. Age-adjusted multivariate analysis identified 'unsuccessful PCI', 'vasopressors on admission' and 'start of ACLS after6 min' as independent predictors of negative long-term outcome (death or CPC2).Mortality is high in patients with STEMI complicated by OHCA - even though PCI was performed with the same success rate as in patients without OHCA. The majority of survivors had favourable neurological outcomes at 1 year, especially if advanced life support had been started within ≤6 min and PCI was successful.

Inflammation plays a crucial role in the pathophysiology of atherosclerosis. Besides cytokines, chemokines and cell adhesion molecules, CD40 and P-selectin play important roles as key regulators of the inflammatory process in atherosclerosis. Danshen (DS) is commonly used in traditional Chinese medicine for therapy of cardiovascular diseases such as coronary artery disease. The aim of the present study was to evaluate the protective effects of DS with respect to possible anti-inflammatory effects. Human umbilical vein endothelial cells as well as platelets were incubated with an extract of DS or one of its major ingredients salvianolic acid B (Sal B), tanshinone IIA (Tansh) and protocatechuic acid (Protoc) under tumor necrosis factor (TNF)-α or ADP stimulation. Expression of CD40 and cellular adhesion molecules (VCAM-1/ICAM-1) were assessed via flow cytometry. Levels of interleukin (IL)-6, IL-8, monocyte-chemoattractant-protein (MCP)-1 as well as soluble VCAM1 and ICAM-1 in the supernatants were examined via luminex based analysis. Treatment with DS attenuated TNF-α induced expression of CD40. Furthermore, the expression of VCAM-1 and ICAM-1 as well as the release of soluble VCAM-1 and ICAM-1 were downregulated. In the cell supernatants we also observed a significant reduction of IL-6, IL8 and MCP-1. DS and its major ingredients, Sal B and Protoc, significantly inhibited TNF-induced expression and release of adhesion molecules, cytokines and chemokines as well as ADP-induced expression of platelet P-selectin. Because of the key roles of inflammatory mediators in the etiology of atherosclerosis, this work provides useful insight in understanding the pharmacological efficacy of Chinese herbal medicine.

Introduction: There is growing evidence that inflammation plays a pivotal role in the etiology and progression of atherosclerosis. High C-reactive protein (CRP) levels have been associated with high mortality in patients with acute myocardial infarction (AMI). Furthermore, in animal models CRP has been found to significantly increase infarct size. So there is growing evidence that CRP is not only a marker for cardiovascular disease but also might be pathogenic. The aim of our study was to test the hypothesis that peak CRP levels could predict heart failure (HF) in ST-elevation myocardial infarction (STEMI) patients. Material and methods: Eighty-one consecutive patients with STEMI were prospectively enrolled in the study. C-reactive protein concentrations were measured on admission and after 6, 12, 24, 30, 48, 72 and 96 h. We assessed the association between the elevation of CRP, heart failure and cardiovascular mortality following the first 12 months after STEMI. Results: C-reactive protein levels reached a peak after 48 h. Patients with STEMI and signs of HF showed significantly higher peak CRP levels. We found a positive correlation between maximum CK levels and peak CRP and a negative correlation between left ventricular ejection fraction (EF) and peak CRP. One year total mortality and HF mortality rates were found to be higher in patients with peak CRP > 47.5 mg/l than in those with CRP below that level (p < 0.001). Conclusions: Peak CRP levels in STEMI patients predict emergence of HF. Peak CRP is also a strong predictor of global and cardiovascular mortality during the following year after STEMI.

Background Coronary artery calcification (CAC) is a marker for the presence and extent of coronary atherosclerotic plaques and can be detected non-invasively by multi-detector row CT (MDCT). Well known predictors of CAC are age, gender, and the classical atherogenic risk factors. CAC is associated with atherosclerotic plaque burden, but it is still elusive if atherosclerosis-relevant cytokines and chemokines are also associated with CAC. Methods We conducted a clinical study among 455 consecutive individuals who underwent coronary calcium assessment performed by MDCT. Before MDCT, blood was drawn and subsequently analyzed for 20 different atherosclerosis-relevant cytokines and chemokines using a Luminex-laser-based fluorescence analysis. Results Using univariate analyses, CAC patients revealed significantly higher levels of the chemokines IP-10 (P = 0.047) and eotaxin (P = 0.031) as compared to non-CAC patients. In multivariate analyses using common thresholds for calcium burden, the three cytokines interleukin-6 (P = 0.028), interleukin-8 (P = 0.009), and interleukin-13 (P = 0.024) were associated with high coronary calcium levels after adjustment for classical variables and risk factors. Conclusions In a large group of individuals with atypical chest pain and a low to intermediate likelihood for coronary artery disease elevated plasma levels of IL-6 and reduced levels of IL-8 and IL-13 were predictive for distinct coronary artery calcification. These findings support a specific role of these cytokines in coronary calcification.

Growing evidence shows that inflammation has a pivotal role in the pathophysiology of essential hypertension (EH). Although it has been acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages, but T lymphocytes have recently become the center of interest. The goal of our study was to evaluate the role of T-cell-specific cytokines in the pathogenesis of EH. The study examined 39 patients with EH (57.7±6.8 years, systolic blood pressure (SBP) 157.5±11.8 mm Hg, diastolic blood pressure 92.2±12.9 mm Hg, mean arterial pressure 113.9±12.6 mm Hg) and 30 healthy, normotensive controls (55.2±4.9 years). Blood was drawn from a peripheral vein, and serum levels of interferon-inducible protein (IP)-10 and interleukins (IL)-4, -7 and -13 were measured by a multiplexing assay. Hypertensive patients had significantly higher levels of IP-10, IL-4, IL-7 and IL-13 than control subjects. When the patients were classified into tertiles according to their serum IP-10 levels (T1: 41.2-94.1 pg ml(-1); T2: 103.4-162.5 pg ml(-1); T3: 171.7-443.5 pgml(-1)), the patients classified into the highest tertile also had the highest blood pressure. In a correlation analysis, plasma IP-10 concentration was significantly associated with SBP (r=0.59, P

The role of DCs (dendritic cells) as potent mediators of inflammation has not been sufficiently investigated in stroke. Therefore, in the present study, circulating mDCPs (myeloid DC precursors), pDCPs (plasmacytoid DCPs) and tDCPs (total DCPs) were analysed by flow cytometry in (i) healthy controls (n=29), (ii) patients with ACI-S (asymptomatic cerebral infarction stenosis; n=46), (iii) patients with TIA (transient ischaemic attack; n=39), (iv) patients with AIS (acute ischaemic stroke; n=73), and (v) patients with AHS (acute haemorrhagic stroke; n=31). The NIHSS (National Institutes of Health Stroke Scale) and infarction size on a CT (computer tomography) scan were evaluated after stroke. In a patient subgroup, post-mortem immunohistochemical brain analyses were performed to detect mDCs (CD209), pDCs (CD123), T-cells (CD3) and HLA-DR. In AIS and AHS, the numbers of circulating mDCPs (P

Atherosclerosis, as an inflammatory disease, is characterized by pathologically altered levels of cytokines. We investigated whether smoking affects the CD40/CD154 system and pro-inflammatory cytokines in young males without other risk factors for atherosclerosis.Young male smokers (n=13) and 14 non-smoking controls were investigated.The differences in CD40/CD154 system and serum cytokines between the groups were measured using flow cytometry and ELISA.In smokers, there was a strong trend (P0.06) for increased CD40 expression on platelets as compared with non-smokers. However, there were no significant differences in CD40 expression on monocytes or in CD154 expression on platelets and T-cells between smokers and non-smokers. There was a strong trend for increased platelet-monocyte aggregates in smokers (P0.06). Also, smokers had slightly but not significantly elevated hsCRP and IL-6 levels, and slightly decreased TNF-alpha and MCP-1. Interestingly, IL-18, a cytokine which has the ability to promote both Th1 and Th2 responses, was significantly decreased in smokers group (P=0.03 vs controls).In young healthy males, smoking is not associated with dramatic changes in CD40/CD154 system. However, cigarette smoke alters the secreted cytokine profile, leading to significant decrease in systemic IL-18 levels.

Background Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Vascular endothelial cell growth factor (VEGF) is currently discussed as a possible mediator of inflammation. To investigate the hypothesis that VEGF plays a role as an inflammatory mediator in EH we performed the present pilot study of young patients in a very early stage of EH. Materials and methods 15 young patients with mild EH [33·8 ± 7·3 years, systolic blood pressure (SBP): 143·8 ± 10·5 mmHg, diastolic blood pressure (DBP): 88·2 ± 11·1 mmHg, mean arterial pressure (MAP) 106·6 ± 10·4 mmHg] and 15 healthy controls (31·7 ± 10·6 years) were examined. Blood was drawn from a peripheral vein and serum levels of VEGF, monocyte-chemoattractant-protein (MCP)-1, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and tumour-necrosis-factor (TNF)-α were measured via commercially available enzyme-linked immunoassays. Results Hypertensives showed increased plasma levels of VEGF (P

The signal transduction activating extracellular-regulated kinases (ERK) is triggered by G protein-coupled receptors (GPCR). In turn, the GPCR are mediated by G q and G i/o proteins subjected to regulation of regulators of G protein-mediated signaling (RGS) proteins. This network compiles extracellular growth signals to intracellular targets of sclerosis on calcified and stenotic human aortic valves (CSAV). Statins are known as partial inhibitors of atherosclerotic inflammation on CSAV. This study identifies descriptively the role of statins on RGS subjected ERK activation on CSAV. We collected human CSAV with ( n = 10, CSAV+) or without ( n = 10, CSAV−) at least 4 weeks of statin pre-treatment and investigated gene-profiling of RGS proteins, intermediaries and ERK using microarray technique, real-time and semi-quantitative PCR. Human non-calcified aortic valves were controls ( n = 6, C). Immunohistochemical stainings defined activation of expressed ERK 1/2 on CSAV (+/−) or C. As compared to C, in CSAV− several cardiac expressed RGS proteins were translationally upregulated: RGS1 (2.6 compared C), RGS3 (3.1), RGS5 (2.1) and RGS8 (2.5). In CSAV+, statins neutralized observed RGS expression. ERK expression was found unchanged in all valves: CSAV−, CSAV+ or C. In contrast, immunohistochemically we found enhanced activation of phosphorylated ERK in CSAV+ as compared to CSAV− or control. This study shows reduced RGS protein expression through statins leading to increased activation of ERK on human CSAV. In regard to known studies, the partial therapeutical failure of statins on severe end-stage CSAV is due to the induction of ERK activation which offers the need for more investigation.

Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages.

In einer schriftlichen Befragung von knapp 500 Unternehmen der Metropolregion Rhein-Neckar wurde das Angebot familienfreundlicher Maßnahmen und die Sicht der Unternehmen auf das Thema Vereinbarkeit von Familie und Beruf erhoben. Durch eine differenzierte Analyse familienfreundlicher Maßnahmen lassen sich spezifische Einflussfaktoren für die Bereiche Arbeitszeitmodelle, Elternförderung sowie einfacher und aufwendiger Kinderbetreuung herausarbeiten. Neben betrieblichen Merkmalen erweisen sich insbesondere Einstellungen der Personalverantwortlichen bzw. Geschäftsführer/-innen zur Vereinbarkeit und deren Informationsstand als relevante Einflussgrößen auf das Angebot familienfreundlicher Maßnahmen.

Background Increasing scientific data suggests a role for inflammation in chronic heart failure (CHF), but up to now the exact mechanisms are still not clear. Recently, platelets were identified to induce inflammation partly by releasing cytokines. This new aspect necessitates further studies about the contribution of platelets for the inflammatory setting of CHF. Methods 50 CHF patients (66.9 + 12.6 years, mean EF 22.1+9.1 %) and 25 healthy controls (63.6±10.2 years) were examined. MCP-1 serum levels were measured via EIA, expression of platelet CD154 by flow cytometry. In in-vitro experiments activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA. Results CHF patients showed significantly enhanced MCP-1 levels (median: 191.8; 25th: 153.7; 75th: 227.1 pg/mL vs. median: 101.0 25th: 86.7; 75th: 117.5 pg/mL, p

Sclerotic calcification of the aortic valve is a common disease in advanced age. Its pathophysiology is unclear. However, pathobiological similarities to atherosclerosis have been shown in several studies. The current study assesses gene profiling of severe calcified stenotic human aortic valves identifying transforming growth factor (TGF)-beta, Eotaxin3, vascular adhesion protein-1 (VAP-1) and monokine induced by interferon-gamma (MIG) as potential atherosclerotic target genes in severe calcified and stenotic aortic valves, and analyzes the effects of statins on their expression as part of an anti-inflammatory treatment strategy. We collected human severe calcified and stenotic aortic valves with (CSAV+) or without (CSAV-) statin pre-treatment prior to valve replacement and investigated gene profiling by using micro-array technique and real-time PCR for the TGF-beta, Eotaxin3, VAP-1 and MIG expression. In comparison to atherosclerotic plaques of carotid arteries, immunohistochemical staining was investigated. Results were contrasted to human normal non-calcified aortic valves as controls (C). As compared to C, TGF-beta, Eotaxin3, MIG or VAP-1 was significantly upregulated in CSAV-. In CSAV+ no significant change in gene expression was found for Eotaxin3 and MIG. In contrast, VAP-1 and TGF-beta were still upregulated. Corresponding gene expression was confirmed on atherosclerotic plaque formations of carotid arteries. Monocyte/Macrophage infiltration (presence of CD68) on aortic valves (CSAV+, CSAV-, or C) confirmed inflammatory nature of the disease. Our data support further evidence for atherosclerotic inflammation as a trigger for sclerosis in end-stage calcified stenotic aortic valves by showing upregulation of gene expression for TGF-beta, VAP-1, MIG and Eotaxin3, which is only partially inhibited by previous statin therapy. Potent benefits of statin treatment on early stages of valve disease are still propagated.

Background Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Although it is acknowledged that target organ damage involves an inflammatory response, most work has focused on the role of macrophages. However, recently, platelets were identified as inducing inflammation partly by releasing cytokines. The goal of our study was to evaluate the role of platelets as inflammatory cells in the pathogenesis of EH. Methods Thirty-nine patients with EH and 30 healthy normotensive controls have been examined. Expression of platelet CD40 was measured by flow cytometry. Serum levels of monocyte chemoattractant protein 1 (MCP-1) and sCD40L were measured via a multiplexing assay. In in vitro experiments, activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA. Results Essential hypertension patients showed significantly enhanced MCP-1 levels with highest levels in EH patients with microalbuminuria. EH patients showed increased expression of platelet CD40. In the cell coculture model, activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD40L-dependent manner. EH patients showed elevated sCD40L levels with a positive correlation with MCP-1 levels. Conclusions Platelets can contribute to enhanced MCP-1 levels in EH. MCP-1 is markedly elevated in serum of EH patients with highest levels in patients with microalbuminuria, one early sign of renal target organ damage. Further studies are required to test whether MCP-1 blocking or antiplatelet strategies may represent new therapeutic options in preventing hypertensive target organ damage.

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.

SummaryProlactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically.We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detecteda significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors,21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect,whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.

Statins were shown to possess immunomodulating properties, but the mechanisms of statin effects on the immune system are poorly understood. We analyzed the influence of statins on professional antigen-presenting dendritic cells (DC). Immature DC were cultivated from monocytes of healthy donors. DC maturation was induced by lipopolysaccharide (LPS; 1 μg/mL). Unstimulated and LPS-stimulated DC were treated with simvastatin or atorvastatin (0.1–1 μM). The expression of CD40, CD83, CD86, and human leukocyte antigen-DR on unstimulated and LPS-stimulated DC was reduced significantly by statins, and the expression of Toll-like receptor 2 (TLR2) and TLR4 on LPS-stimulated DC was enhanced temporarily. Statins caused a significant reduction of endocytosis of fluorescein isothiocyanate-dextran by DC. Statins significantly inhibited the basal secretion of interleukin (IL)-6, IL-8, IL-12, and tumor necrosis factor α from unstimulated DC, and their release from LPS-stimulated DC was enhanced. In mixed leukocyte reaction, preincubation of LPS-stimulated DC with statins significantly suppressed their clustering with T cells and their ability to induce T cell proliferation, CD71, and CD25 up-regulation on T cells and the secretion of interferon-γ and IL-2 from T cells. In conclusion, this study showed that statins suppressed endocytosis, basal secretion of proinflammatory cytokines, and the ability of DC to induce T cell proliferation, activation, and T helper cell type 1 differentiation. However, statin preincubation of LPS-stimulated DC caused a further increase in their secretion of proinflammatory cytokines.

Emerging evidence links inflammation to atherosclerosis (AS). Although some studies have addressed the role of inflammation in patients with arterial hypertension (AH), its overall contribution in AH is far from being understood. Therefore, the present pilot study was designed to examine the role of platelet P-selectin and various inflammatory mediators in young patients with moderate AH without signs of target organ damage.Fifteen patients with mild AH [33.8 +/- 7.3 years, mean arterial pressure (MAP) 106.6 +/- 10.4 mmHg] and 15 healthy normotensive controls (31.7 +/- 10.6 years) were examined. Platelet P-selectin was analysed by flow cytometry. Plasma levels of monocyte-chemoattractant-protein-1 (MCP-1), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, tumour necrosis factor alpha (TNFalpha), and IL-10 levels were measured by enzyme immunoassay (EIA). Patients with mild AH showed significantly enhanced expression of platelet P-selectin [17.2 +/- 5.4 versus 10.6 +/- 4.2 mean fluorescence intensity (MFI), P0.001]. P-selectin expression positively correlated with MAP (r = 0.43, P0.05). Furthermore, patients with mild AH had significantly enhanced plasma levels of hsCRP (2.7 +/- 3.8 versus 0.6 +/- 0.9 mg/l, P0.01), IL-6 (1.4 +/- 0.7 versus 0.6 +/- 0.3 pg/ml, P0.001), TNFalpha (2.8 +/- 0.7 versus 2.4 +/- 0.4 pg/ml, P0.05), and MCP-1 (291.3 +/- 100.7 versus 214.3 +/- 8.3 pg/ml, P0.05). IL-6 levels positively correlated with hsCRP levels (r = 0.47, P0.05) and mean arterial pressure (MAP) (r = 0.44, P0.05).This pilot study demonstrates that in an early stage of AH, inflammatory pathways are already activated. Besides pro-inflammatory cytokines, platelets seem to play a significant role in mediating inflammation in AH, which could lead to target organ injury. Further investigations have to clarify the role of early anti-inflammatory therapy, in patients with mild to moderate AH, in alleviating hypertensive target organ damage.

Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcγRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2±12.6%; SAP, 44.9±13.6%; UAP, 28.4±10.1%; AMI, 20.3±8.5%; AMI or UAP vs. SAP or C, P

Background: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-α and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 intitiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. Methods: Fifty patients with CHF (aged 66.9±12.6 years, mean ejection fraction 22.1±9.2%, NYHA II–IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5±9.8 years) were examined. Thirty-two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry. Results: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P

BackgroundHypercholesterolemia, a risk factor for cardiovascular disease, is associated with inflammation and hypercoagulability. Both can be mediated by the CD40 system. This study investigated whether the CD40 system is upregulated in patients with moderate hypercholesterolemia and whether it is influenced by therapy with a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor.Methods and ResultsFifteen patients with moderate hypercholesterolemia and 15 healthy control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 was analyzed on monocytes before and under therapy with the statin cerivastatin by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. Our main findings were as follows. Patients with moderate hypercholesterolemia showed a significant increase of CD154 and P-selectin on platelets and CD40 on monocytes compared with healthy subjects. Soluble CD154 showed a nonsignificant trend for higher plasma levels in patients. A positive correlation was found for total or LDL cholesterol and CD154, but not for CD40 on monocytes. The latter was upregulated in vitro by C-reactive protein, which was found to be significantly elevated in patients with moderate hypercholesterolemia. CD154 on platelets proved to be biologically active because it enhanced the release of MCP-1, which was markedly elevated in an in vitro platelet-endothelial cell coculture model and in the serum of patients. Short-term therapy with a HMG-CoA reductase inhibitor significantly downregulated CD40 on monocytes and serum levels of MCP-1.ConclusionPatients with moderate hypercholesterolemia show upregulation of the CD40 system, which may contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.