Angiogenesis, Metabolism, Endothelial and Platelet Markers in Diabetes and Cardiovascular Disease

Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively

Quasiparticle Lifetime in a Finite System: A Non--Perturbative Approach

The problem of electron--electron lifetime in a quantum dot is studied beyond perturbation theory by mapping it onto the problem of localization in the Fock space. We identify two regimes, localized and delocalized, corresponding to quasiparticle spectral peaks of zero and finite width, respectively. In the localized regime, quasiparticle states are very close to single particle excitations. In the delocalized state, each eigenstate is a superposition of states with very different quasiparticle content. A transition between the two regimes occurs at the energy $\simeq\Delta(g/\ln g)^{1/2}$, where $\Delta$ is the one particle level spacing, and $g$ is the dimensionless conductance. Near this energy there is a broad critical region in which the states are multifractal, and are not described by the Golden Rule.Comment: 13 pages, LaTeX, one figur

Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation

Laboratory assessment of anti-thrombotic therapy in heart failure, atrial fibrillation and coronary artery disease: insights using thrombelastography and a micro-titre plate assay of thrombogenesis and fibrinolysis

As heart failure, coronary artery disease and atrial fibrillation all bring a risk of thrombosis, anti-thrombotic therapy is recommended. Despite such treatment, major cardiovascular events such as myocardial infarction and stroke still occur, implying inadequate suppression of thrombus formation. Accordingly, identification of patients whose haemostasis remains unimpaired by treatment is valuable. We compared indices for assessing thrombogenesis and fibrinolysis by two different techniques in patients on different anti-thrombotic agents, i.e. aspirin or warfarin. We determined fibrin clot formation and fibrinolysis by a microplate assay and thromboelastography, and platelet marker soluble P selectin in 181 patients with acute or chronic heart failure, coronary artery disease who were taking either aspirin or warfarin. Five thromboelastograph indices and four microplate assay indices were different on aspirin versus warfarin (p < 0.05). In multivariate regression analysis, only microplate assay indices rate of clot formation and rate of clot dissolution were independently related to aspirin or warfarin use (p ≤ 0.001). Five microplate assay indices, but no thrombelastograph index, were different (p < 0.001) in aspirin users. Three microplate assay indices were different (p ≤ 0.002) in warfarin users. The microplate assay indices of lag time and rate of clot formation were abnormal in chronic heart failure patients on aspirin, suggesting increased risk of thrombosis despite anti-platelet use. Soluble P selectin was lower in patients on aspirin (p = 0.0175) but failed to correlate with any other index of haemostasis. The microplate assay shows promise as a tool for dissecting thrombogenesis and fibrinolysis in cardiovascular disease, and the impact of antithrombotic therapy. Prospective studies are required to determine a role in predicting thrombotic risk

Particle-hole state densities with non-equidistant single-particle levels

The correct use of energy-dependent single-particle level (s.p.l.) densities within particle-hole state densities based on the equidistant spacing model (ESM) is analysed. First, an analytical expression is obtained following the convolution of energy-dependent excited-particle and hole densities. Next, a comparison is made with results of the ESM formula using average s.p.l. densities for the excited particles and holes, respectively. The Fermi-gas model (FGM) s.p.l. densities calculated at the corresponding average excitation energies are used in both cases. The analysis concerns also the density of particle-hole bound states. The pairing correlations are taken into account while the comparison of various effects includes the exact correction for the Pauli exclusion principle. Quantum-mechanical s.p.l. densities and the continuum effect can also match a corresponding FGM formula, suitable for use within the average energy-dependent partial state density in multistep reaction models.Comment: 29 pages, ReVTeX, 11 postscript figures, submitted to Phys.Rev.

Proton inelastic scattering to continuum studied with antisymmetrized molecular dynamics

Intermediate energy (p,p$'$x) reaction is studied with antisymmetrized molecular dynamics (AMD) in the cases of $^{58}$Ni target with $E_p = 120$ MeV and $^{12}$C target with $E_p =$ 200 and 90 MeV. Angular distributions for various $E_{p'}$ energies are shown to be reproduced well without any adjustable parameter, which shows the reliability and usefulness of AMD in describing light-ion reactions. Detailed analyses of the calculations are made in the case of $^{58}$Ni target and following results are obtained: Two-step contributions are found to be dominant in some large angle region and to be indispensable for the reproduction of data. Furthermore the reproduction of data in the large angle region \theta \agt 120^\circ for $E_{p'}$ = 100 MeV is shown to be due to three-step contributions. Angular distributions for E_{p'} \agt 40 MeV are found to be insensitive to the choice of different in-medium nucleon-nucleon cross sections $\sigma_{NN}$ and the reason of this insensitivity is discussed in detail. On the other hand, the total reaction cross section and the cross section of evaporated protons are found to be sensitive to $\sigma_{NN}$. In the course of the analyses of the calculations, comparison is made with the distorted wave approach.Comment: 16 pages, 7 Postscript figure

Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?

Background: Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Materials and methods: Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Results: Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng m