CD40 ligand inhibits endothelial cell migration by increasing production of endothelial reactive oxygen species

Background— The CD40/CD40 ligand system is involved in atherogenesis. Activated T lymphocytes and platelets, which express high amounts of CD40 ligand (CD40L) on their surface, contribute significantly to plaque instability with ensuing thrombus formation, leading to acute coronary syndromes. Because reendothelialization may play a pivotal role for plaque stabilization, we investigated a potential role of CD40L on endothelial cell (EC) migration

Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells

Background— Transplantation of ex vivo expanded circulating endothelial progenitor cells (EPCs) from peripheral blood mononuclear cells improves the neovascularization after critical ischemia. However, the origin of the endothelial progenitor lineage and its characteristics have not yet been clearly defined. Therefore, we investigated whether the phenotype and functional capacity of EPCs to improve neovascularization depend on their monocytic origin

Nicotine strongly activates dendritic cell-mediated adaptive immunity - potential role for progression of atherosclerotic lesions

Background - Antigen-presenting cells (APCs) such as monocytes and dendritic cells (DCs) stimulate T-cell proliferation and activation in the course of adaptive immunity. This cellular interaction plays a role in the growth of atherosclerotic plaques. Nicotine has been shown to increase the growth of atherosclerotic lesions. Therefore, we investigated whether nicotine can stimulate APCs and their T cell–stimulatory capacity using human monocyte–derived DCs and murine bone marrow–derived DCs as APCs. Methods and Results - Nicotine dose-dependently (10-8 to 10-4 mol/L) induced DC expression of costimulatory molecules (ie, CD86, CD40), MHC class II, and adhesion molecules (ie, LFA-1, CD54). Moreover, nicotine induced a 7.0-fold increase in secretion of the proinflammatory TH1 cytokine interleukin-12 by human DCs. These effects were abrogated by the nicotinic receptor antagonist -bungarotoxin and mecamylamine, respectively. The effects of nicotine were mediated in part by the phosphorylation of the PI3 kinase downstream target Akt and the mitogen-activated kinases ERK and p38 MAPK. Nicotine-stimulated APCs had a greater capacity to stimulate T-cell proliferation and cytokine secretion, as documented by mixed lymphocyte reactions and ovalbumin-specific assays with ovalbumin-transgenic DO10.11 mice. In a murine model of atherosclerosis, nicotine significantly enhanced the recruitment of DCs to atherosclerotic lesions in vivo. Conclusions - Nicotine activates DCs and augments their capacity to stimulate T-cell proliferation and cytokine secretion. These effects of nicotine may contribute to its influence on the progression of atherosclerotic lesions

Low-energy shock wave for enhancing recruitment of endothelial progenitor cells: a new modality to increase efficacy of cell therapy in chronic hind limb ischemia

Background— Stem and progenitor cell therapy is a novel approach to improve neovascularization and function of ischemic tissue. Enhanced tissue expression of chemoattractant factors such as stromal cell–derived factor 1 and vascular endothelial growth factor is crucial for the recruitment of circulating endothelial progenitor cells (EPCs) during acute ischemia. In chronic ischemia, however, expression of these chemoattractants is less pronounced, which results in insufficient EPC recruitment into the target tissue. Therefore, we investigated the effect of targeted extracorporeal shock wave (SW) application in order to facilitate EPC recruitment into nonischemic and chronic ischemic tissue

Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease

Background - Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia. Circulating bone marrow–derived endothelial progenitor cells (EPCs) were shown to augment the neovascularization of ischemic tissue. In addition to lipid-lowering activity, hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals. Methods and Results - Fifteen patients with angiographically documented stable coronary artery disease (CAD) were prospectively treated with 40 mg of atorvastatin per day for 4 weeks. Before and weekly after the initiation of statin therapy, EPCs were isolated from peripheral blood and counted. In addition, the number of hematopoietic precursor cells positive for CD34, CD133, and CD34/kinase insert domain receptor was analyzed. Statin treatment of patients with stable CAD was associated with an '1.5-fold increase in the number of circulating EPCs by 1 week after initiation of treatment; this was followed by sustained increased levels to '3-fold throughout the 4-week study period. Moreover, the number of CD34/kinase insert domain receptor–positive hematopoietic progenitor cells was significantly augmented after 4 weeks of therapy. Atorvastatin treatment increased the further functional activity of EPCs, as assessed by their migratory capacity

Vitamin C inhibits endothelial cell apoptosis in congestive heart failure

Background - Proinflammatory cytokines like tumor necrosis factor- and oxidative stress induce apoptotic cell death in endothelial cells (ECs). Systemic inflammation and increased oxidative stress in congestive heart failure (CHF) coincide with enhanced EC apoptosis and the development of endothelial dysfunction. Therefore, we investigated the effects of antioxidative vitamin C therapy on EC apoptosis in CHF patients. Methods and Results - Vitamin C dose dependently suppressed the induction of EC apoptosis by tumor necrosis factor- and angiotensin II in vitro as assessed by DNA fragmentation, DAPI nuclear staining, and MTT viability assay. The antiapoptotic effect of vitamin C was associated with reduced cytochrome C release from mitochondria and the inhibition of caspase-9 activity. To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32±8% of baseline levels, whereas placebo had no effect (87±14%, P<0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients (P<0.001). Conclusions - Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function

A subradiant optical mirror formed by a single structured atomic layer

Efficient and versatile interfaces for the interaction of light with matter are an essential cornerstone for quantum science. A fundamentally new avenue of controlling light-matter interactions has been recently proposed based on the rich interplay of photon-mediated dipole-dipole interactions in structured subwavelength arrays of quantum emitters. Here we report on the direct observation of the cooperative subradiant response of a two-dimensional (2d) square array of atoms in an optical lattice. We observe a spectral narrowing of the collective atomic response well below the quantum-limited decay of individual atoms into free space. Through spatially resolved spectroscopic measurements, we show that the array acts as an efficient mirror formed by only a single monolayer of a few hundred atoms. By tuning the atom density in the array and by changing the ordering of the particles, we are able to control the cooperative response of the array and elucidate the interplay of spatial order and dipolar interactions for the collective properties of the ensemble. Bloch oscillations of the atoms out of the array enable us to dynamically control the reflectivity of the atomic mirror. Our work demonstrates efficient optical metamaterial engineering based on structured ensembles of atoms and paves the way towards the controlled many-body physics with light and novel light-matter interfaces at the single quantum level.Comment: 8 pages, 5 figures + 12 pages Supplementary Infomatio