0000000000042520
AUTHOR
Axel Schlitt
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…
Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury
Background and purpose: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. Experimental approach: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10 000 Ukg−1) or its vehicle were injected 5 min prior to the start of reperfusion. Key results: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11±2.7% necrosis as percentage of area at risk aft…
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…
Clopidogrel and aspirin in the prevention of thromboembolic complications after mechanical aortic valve replacement (CAPTA)
Axel Schlitt*, Ralf S. von Bardeleben, Anne Ehrlich, Antje Eimermacher, Dirk Peetz, Manfred Dahm, Hans J. Rupprecht Department of Medicine II, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany Coordination Center for Clinical Studies, Johannes Gutenberg-University Mainz, Mainz, Germany Clinic for Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Mainz, Mainz, Germany Department of Cardiothoracic and Vascular Surgery, Johannes Gutenberg-University Mainz, Mainz, Germany
Cholesteryl ester transfer protein activity and cardiovascular events in patients with chronic kidney disease stage V.
Background Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular events (CVE). Uraemic dyslipidaemia, which is characterized by low HDL-cholesterol (HDL-C) and elevated triglycerides' levels, may contribute to this elevated cardiovascular risk. Cholesteryl ester transfer protein (CETP) lowers HDL-C by transferring cholesterol esters to LDL and VLDL particles. We tested the hypothesis that CETP activity is associated with CVE in patients with CKD stage V. Methods We measured CETP activity and cholesterol levels in 69 haemodialysis patients. CVE and death were prospectively assessed over a follow-up period of 48 months. Results CETP activity was negatively corre…
Effects of combined therapy of clopidogrel and aspirin in preventing thrombus formation on mechanical heart valves in an ex vivo rabbit model.
Abstract Background: The aim of our study was to investigate the efficacy of the combination of clopidogrel and aspirin in the prevention of thrombus formation on artificial heart valves in an experimental rabbit model as compared to anticoagulation with warfarin. Methods: Studies were performed after oral administration of clopidogrel and aspirin in group I (n=9) for 5 days, after 5±2 days treatment with warfarin in group II (n=9) and without medication in group III (n=9). Leaflets from Sulzer Carbomedics bileaflet 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. Results: In group III, …
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…
Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation
Background and purpose: The Na+/H+ exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca2+ overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. Experimental approach: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 μ ml−1) superfusion or ischaemia (by haemorrhagic shock…
Neutrophil Adherence to Activated Saphenous Vein and Mammary Endothelium After Graft Preparation
Interaction of circulating leukocytes and vascular endothelium plays an important role in vasoconstriction, endothelial dysfunction, and vascular injury. Dilation procedures of grafts before coronary artery bypass graft surgery might lead to vascular injury and subsequent bypass graft disease.We analyzed in vitro the adherence of fluorescence-labeled polymorphonuclear neutrophils (PMNs) to endothelium of human saphenous vein grafts or internal mammary artery grafts after stimulation with thrombin (0.5 to 2 U/mL) or dilating procedures. Furthermore, we investigated endothelial function of prepared grafts.Thrombin stimulation resulted in a dose-dependent increase of PMN adherence to the endot…
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…
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…
Einfluss genetischer Variationen des Cholesterylestertransferproteingens auf die Pr�valenz der koronaren Herzerkrankung
Mehrere funktionelle Polymorphismen des Cholesterylestertransferprotein( CETP)-Gens beeinflussen die CETP-Aktivitat und die High-density-lipoprotein(HDL)-Cholesterin-Konzentration. Neben anderen funktionellen Varianten wird vornehmlich der Promotorpolymorphismus CETP/C-629A als Risikofaktor der koronaren Herzerkrankung (KHK) diskutiert. Wir untersuchten in einer grosen Fall-/Kontroll-Studie den Einfluss verschiedener CETP-Genotypen und Haplotypen auf die HDL-Konzentration sowie die Pravalenz der KHK. Bei 1214 Patienten mit dokumentierter KHK sowie 574 Populationskontrollen wurden neben den klassischen Risikofaktoren folgende CETP-Polymorphismen bestimmt: C-629A, TaqIB, I405V, R451Q und A373…
Relation of markers of inflammation (C-reactive protein, fibrinogen, von Willebrand factor, and leukocyte count) and statin therapy to long-term mortality in patients with angiographically proven coronary artery disease
We evaluated a possible interaction between statins and inflammation in 1,246 patients with angiographically diagnosed coronary artery disease. Four different inflammatory markers were determined: high, sensitive C-reactive protein (hs-CRP) (p = 0.001), fibrinogen (p = 0.006), von Willebrand factor (p = 0.006), and leukocyte count (p = 0.03); these levels were significantly higher among the 88 patients who died of cardiac causes during follow-up (median 2.9 years) than among survivors. In a multivariate backward stepwise Cox regression mode, only hs-CRP was evaluated to be a significant predictor of death from coronary artery disease. This prediction was lost in statin-treated patients. Com…
Monocyte-derived dendritic cells of patients with coronary artery disease show an increased expression of costimulatory molecules CD40, CD80 and CD86 in vitro.
Background Atherosclerosis is a disease triggered by diverse exogenous stimuli and sustained by chronic inflammatory processes. Dendritic cells (DCs) are key regulatory antigen-presenting cells and play a crucial role in regulating the adaptive and innate immune system in any chronic inflammatory process. DCs are present in atherosclerotic lesions in the areas of the highest T-cell density. So far, their role in atherosclerosis has not been fully elucidated. We investigated the phenotypic properties of DCs in patients with coronary artery disease (CAD) in comparison to healthy individuals. Methods Peripheral blood monocytes were isolated from 50 patients with CAD and 19 healthy individuals …
PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene study.
Phospholipid transferprotein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Although many studies have investigated the role of PLTP in atherogenesis, the role of PLTP in atherosclerotic diseases is unclear. We investigated the association of serum PLTP activity with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and its relation to other markers of atherosclerosis in 1,085 patients with angiographically documented coronary artery disease (CAD). In the median follow-up of 5.1 years, 156 patients had suffered from the combined endpoint of myocardial infarction or cardiovascular death including 47 of 395 p…