0000000000042523
AUTHOR
Juergen Meyer
CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels
SummaryMonocytes play a central role in the inflammatory disease atherosclerosis. CD14+CD16+ monocytes are considered proinflammatory monocytes, as they have an increased capacity to produce proinflammatory cytokines, such as TNF-α, and are elevated in various inflammatory diseases. We hypothesized that patients with coronary artery disease (CAD) have increased levels of CD14+CD16+ monocytes, and that CD14+CD16+ monocytes are associated with inflammation markers. We investigated CD14+CD16+ monocytes in 247 patients with CAD and 61 control subjects using flow cytometry. In addition serum concentrations of TNF-α, IL-6, and Hs-CRP were assessed. Patients with CAD had higher levels of CD14+CD16…
Improvement of tricuspid regurgitation after pulmonary thromboendarterectomy
For patients with chronic thromboembolic pulmonary hypertension who undergo pulmonary thromboendarterectomy (PTE) it has not yet been systematically investigated how operation affects the severity of tricuspid regurgitation (TR). This study sought (1) to evaluate the extent of TR reversibility after operation, (2) to identify potential predictors of the reversibility of TR, and (3) to investigate the influence of geometric and hemodynamic alterations on the extent of TR severity.Thirty-nine patients (55+/-12 years) undergoing PTE without tricuspid valve repair were investigated before and 13+/-8 days after operation by Doppler color flow mapping. Geometry of the tricuspid valve as well as r…
Synergistic Platelet Inhibitory Effect of the Phosphodiesterase Inhibitor Piroximone and Iloprost
Platelet activity is regulated through synthesis and degradation of the intracellular second messengers cAMP or cGMP. The antiplatelet effect of the phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50 of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of platelet count following injection of 100 micrograms/kg bw collagen was measured after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in …
Pathophysiology of Impaired Right and Left Ventricular Function in Chronic Embolic Pulmonary Hypertension
Study objectives: This study sought to evaluatethe pathophysiology of left and right heart failure in patients withchronic thromboembolic pulmonary hypertension (CTEPH) who werehospitalized to undergo pulmonary thromboendarterectomy (PTE). Design: Thirty-nine patients (16 women and 23 men;mean ± SD age, 55 ± 12 years) with severe CTEPH were examinedbefore and 13 ± 8 days after PTE by way of transthoracicechocardiography and right heart catheterization. Measurements and results: Examination resultsconfirmed in all cases that before surgery the right ventricles wereenlarged and systolic function was impaired. Moderate to severetricuspid valve regurgitation was observed. Left ventriculareccent…
Increase in Endogenous Fibrinolysis and Platelet Activity during Exercise in Young Volunteers
Physicians at the Medical Clinic at the Johannes Gutenberg University in Mainz Germany compared data on 6 18-35 year old healthy women who took low-dose estrogen oral contraceptives (OCs) with data on 10 healthy women of same age who did not take OCs and with data on 12 18-35 year old males to examine gender differences of the coagulation system endogenous fibrinolytic activity and platelet aggregation under normal conditions and immediately after spiroergometric exercise beyond the anaerobic threshold. This type of exercise considerably boosted tissue plasminogen activator (t-PA) in both men and women (1.6-5.5 IU/ml and 1.8-5.3 IU/ml respectively; p < .005). The increase was not as high in…
High Plasma Phospholipid Transfer Protein Levels as a Risk Factor for Coronary Artery Disease
Objective— Plasma phospholipid transfer protein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Animal studies have shown that it is closely related to the development of atherosclerosis. PLTP-deficient mice have demonstrated increased antioxidation potential as well as a decrease in apolipoprotein B secretion and atherosclerotic lesions. In humans, high PLTP is associated with type II diabetes and obesity. Methods and Results— To assess the relationship between PLTP activity and coronary artery disease (CAD), a novel, high-throughput method to measure plasma PLTP activity was used, relating it to CAD in 1102 cases and 444 controls. This demo…
Fondaparinux and enoxaparin in comparison to unfractionated heparin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model
SummaryThe aim of the present study was to investigate the efficacy of three different parenterally administered anticoagulants for the prevention of thrombus formation on artificial heart valves in an experimental rabbit model.Unfractionated heparin was administered intravenously in group I (n = 10), Enoxaparin subcutaneously in group II (n = 10), fondaparinux intravenously in group III (n = 10), and no medication was administered to group IV (n = 9). Leaflets from Sulzer Carbomedics bileaflet mechanical heart valves were placed in a flow chamber. The flow chamber was filled with blood in a continuous circulation between the carotid artery and the jugular vein.In group IV the flow chamber …
Herpesvirus DNA (Epstein-Barr virus, herpes simplex virus, cytomegalovirus) in circulating monocytes of patients with coronary artery disease
Background -The underlying mechanism of the chronic inflammatory process in atherosclerosis is still unknown. As a possible trigger, several studies in recent years have suggested that different viruses and bacteria are associated with atherosclerotic diseases. Methods - We applied polymerase chain reaction to analyse whether Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV) DNA could be detected in CD14 + cells from 184 patients with angiographically documented coronary artery disease (CAD) (74 patients with stable angina (SAP), 51 patients with unstable angina (UAP), and 59 patients with myocardial infarction (Ml)) and from 52 healthy controls. Results - In t…
Assessment of cardiac performance using Tei indices in patients undergoing pulmonary thromboendarterectomy.
This study was designed to evaluate left and right ventricular performance using Tei indices in patients with severe chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy (PTE). The Doppler-derived indices are easily measurable indicators of ventricular function based on nongeometric assessment, which helps overcome some of the difficulties entailed in the geometric assessment of left ventricular (LV) and right ventricular (RV) function in pulmonary hypertension.The indices were derived for 24 patients (aged 54+/-14 years) before and after PTE. Calculation of these indices was based on the duration of two time intervals using the formula (A - B)/B, where A…
Involvement of PKC and NF-κB in Nitric Oxide Induced Apoptosis in Human Coronary Artery Smooth Muscle Cells
Apoptosis of vascular smooth muscle cells is critically involved in progression of atherosclerosis and may prevent intimal hyperplasia in restenosis and vascular remodeling. Nitric oxide (NO) is known to induce apoptosis, but the signaling pathways still remain unclear. We investigated p53 accumulation, protein kinase C (PKC) activation and nuclear transcription factor (NF-kappaB) binding activity as possible signaling mechanisms of NO-induced apoptosis. Apoptosis was induced dose-dependently with the NO-donors sodiumnitroprusside (SNP: 232+/-48%) and SIN-1 (241+/-90% of actinomycin D induced apoptosis; means +/- SEM, *por =0.05 vs. control) in HSMC. Inhibition of PKC significantly attenuat…
Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease
Abstract Background Sphingomyelin (SM) is the major phospholipid in cell membranes and in lipoproteins. In human plasma, SM is mainly found in atherogenic lipoproteins; thus, high levels of SM may promote atherogenesis. Methods We investigated in a median follow up of 6.0 years the association of SM with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) in stable and unstable patients, and its relation to other marker of atherosclerosis in 1,102 patients with angiographically documented CAD and 444 healthy controls. Results and discussion Logistic regression analysis showed that SM categorized by median was associated with an elevated risk for CAD (HR 3.2…
Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging.
BACKGROUND: Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses. METHODS: Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA i…
Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles.
It is known that sphingomyelin (SM) content is higher in apolipoprotein B-containing particles (BLps) than in high density lipoproteins and that BLp levels, including chylomicrons and their remnant particles, are positively related to atherosclerosis. To evaluate the relationship between serum SM and postprandial remnant particle levels, we determined SM, triglyceride (TG), and cholesterol levels in serum and in remnant-like particles (RLPs) before and 3, 5, 7, and 10 h after a high-fat meal in 31 healthy subjects. We found that serum SM, like serum TG, was increased to its maximum 3 h after fat loading and then gradually decreased to basal levels after 10 h. More important, we determined t…
Lokale Medikamentengabe und Gentherapie
Eines der wichtigsten Probleme der klinischen Kardiologie, die Entwickung einer Restenose nach koronarer Ballonangioplastie, ist bisher noch nicht befriedigend gelöst. Die pathophysiologischen Erkenntnisse über die Mechanismen der Neointimabildung sind noch unvollständig, und zahlreiche Therapiestudien mit systemisch applizierten Pharmaka mit unterschiedlichem Wirkungsmechanismus sind fehlgeschlagen. Mögliche innovative Therapieansätze betreffen die hochdosierte lokale Substanzapplikation an der Dilatationsstelle und lokale gentherapeutische Eingriffe zur Verhinderung der Neointimabildung durch Proliferationshemmung der glatten Gefäßmuskelzellen. Zahlreiche Kathetermodelle sind entwickelt w…
Platelet-activating factor type activity in plasma from patients with septicemia and other diseases
The purpose of the present study was to determine whether increased levels of platelet-activating factor (PAF) type activity can be detected in plasma from patients with septicemia and other diseases. A level of PAF below 0.5 ng/mL of plasma was considered normal. We found that plasma from a patient with adverse anaphylactoidic reaction to intravenous analgetics contained 2.1 ng PAF/mL. In seven patients with septicemia, including urosepsis, endocarditis and peritonitis, and with positive blood culture, increased plasma PAF levels (1-20 ng PAF/mL) were observed. Other patients with clinical indications of septicemia had negative blood cultures and/or increased levels of C-reactive protein (…
Prognostic value of lipoproteins and their relation to inflammatory markers among patients with coronary artery disease
Abstract Background Lipoproteins and their subfractions are associated with the incidence of atherosclerotic diseases. In patients with coronary artery disease (CAD), low serum concentrations of high density lipoprotein (HDL) and high low-density lipoproteins (LDL) are correlated to myocardial infarction and cardiovascular death. There is growing evidence indicating that those lipoprotein factors are related to the inflammatory process in atherogenesis. Methods We investigated in a median follow up of 3.9 years the association of HDL, apolipoprotein A-I (apoA-I), LDL, apolipoprotein B (apoB), and triglycerides with the incidence of a combined endpoint (myocardial infarction and cardiovascul…
Diminished Inhibition of Adhesion Molecule Expression in Prostacyclin Receptor Desensitized Human Platelets
Long-term exposure of platelets to prostacyclin or iloprost (100nM, 3hr) results in receptor desensitization measured as decrease in 3H-iloprost binding sites by 47 +/- 14%. Desensitized platelets respond with an increased adhesion to endothelial cells. The mechanism of increased adhesiveness was studied by measuring the expression of the adhesion molecule CD62p (p-selectin; GMP140) on washed human platelets by flowcytometry. In thrombin stimulated platelets CD62p expression was dose-dependently reduced by iloprost. In receptor desensitized platelets IC50 for iloprost inhibition of thrombin-induced CD62p expression increased from 0.48 +/- 0.10 to 2.4 +/- 0.7 nM.