Commentary: Indoleamine 2,3-Dioxygenase-Expressing Aortic Plasmacytoid Dendritic Cells Protect against Atherosclerosis by Induction of Regulatory T Cells.

No abstract available

Способы повышения прочности алюмосиликатной керамики на основе сухарного глинистого сырья

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of atherosclerosis. The CD40-CD40L dyad is known to interact with other co-stimulatory molecules, to activate antigen-presenting cells (APC) and to contribute to T-cell priming and B-cell isotype switching. Besides their presence on T-cells and APCs, CD40 and CD40L are also present on macrophages, endothelial cells and vascular smooth muscle cells in the plaque, where they can exert pro-atherogenic functions. Moreover, recent progress indicates the involvement of neutrophil CD40, platelet CD40L and dendritic cell CD40 in atherogenesis. Since systemic CD40-CD40L modulation compromises host defense, more targeted interventions are needed to develop superior treatment strategies for atherosclerosis. We believe that by unravelling the cell-cell CD40-CD40L interactions, inhibition of cell-type specific (signalling components of) CD40(L) that do not compromise the patient's immune system, will become possible. In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosi

The renewable energy and energy efficiency potential of Waitakere City : a thesis presented in partial fulfilment of the requirements for the degree of Masters of Technology in Energy Management at Massey University

Electricity restrictions and blackouts have occurred in Waitakere City in the past and are likely to occur again in the future unless the city can become more self reliant by meeting, at least in part, the increasing energy requirements for what is one of the fastest growing cities in New Zealand. In this study the potentials for energy conservation, energy efficiency and renewable energy resources have been broadly quantified and assessed using desktop analysis of publicly available data for stationary final use energy systems (i.e. excluding transportation) within the geographical area of Waitakere City and adjoining waters. It was found that energy efficiency and energy conservation measures can consistently and predictably achieve overall energy savings and reduce daily and seasonal peak demand. The best renewable energy resource potential exists with solar and geothermal for heating applications and wave, offshore and inshore wind and tidal currents for electricity generation. There is very limited potential for hydro and bioenergy systems beyond what already exists. PV solar and land based wind power generation are currently only feasible for limited off-grid applications. This scoping study confirms the achievability of the vision expressed in Waitakere City Council's "Long Term Council Community Plan" (LTCCP) that by 2020 " Waitakere City will be an energy cell, not an energy sink. Air quality supports good health". A range of flagship projects have been identified to progress the achievement of this vision. Waitakere City Council can use this report as part of the development of a comprehensive energy management plan

Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease

MicroRNAs (miRNAs) are short sequences of non-coding RNA that play an important role in the regulation of gene expression and thereby in many physiological and pathological processes. Furthermore, miRNAs are released in the extracellular space, for example in vesicles, and are detectable in various biological fluids, such as serum, plasma, and urine. Over the last years, it has been shown that miRNAs are crucial in the development of several cardiovascular diseases (CVDs). This review discusses the (patho)physiological implications of miRNAs in CVD, ranging from cardiovascular risk factors (i.e., hypertension, diabetes, dyslipidemia), to atherosclerosis, myocardial infarction, and cardiac remodeling. Moreover, the intriguing possibility of their use as disease-specific diagnostic and prognostic biomarkers for human CVDs will be discussed in detail. Finally, as several approaches have been developed to alter miRNA expression and function (i.e., mimics, antagomirs, and target-site blockers), we will highlight the miRNAs with the most promising therapeutic potential that may represent suitable candidates for therapeutic intervention in future translational studies and ultimately in clinical trials. All in all, this review gives a comprehensive overview of the most relevant miRNAs in CVD and discusses their potential use as biomarkers and even therapeutic targets

Proteomic-biostatistic integrated approach for finding the underlying molecular determinants of hypertension in human plasma

Despite advancements in lowering blood pressure, the best approach to lower it remains controversial because of the lack of information on the molecular basis of hypertension. We, therefore, performed plasma proteomics of plasma from patients with hypertension to identify molecular determinants detectable in these subjects but not in controls and vice versa. Plasma samples from hypertensive subjects (cases; n=118) and controls (n=85) from the InGenious HyperCare cohort were used for this study and performed mass spectrometric analysis. Using biostatistical methods, plasma peptides specific for hypertension were identified, and a model was developed using least absolute shrinkage and selection operator logistic regression. The underlying peptides were identified and sequenced off-line using matrix-assisted laser desorption ionization orbitrap mass spectrometry. By comparison of the molecular composition of the plasma samples, 27 molecular determinants were identified differently expressed in cases from controls. Seventy percent of the molecular determinants selected were found to occur less likely in hypertensive patients. In cross-validation, the overall R(2) was 0.434, and the area under the curve was 0.891 with 95% confidence interval 0.8482 to 0.9349, P<0.0001. The mean values of the cross-validated proteomic score of normotensive and hypertensive patients were found to be -2.007±0.3568 and 3.383±0.2643, respectively, P<0.0001. The molecular determinants were successfully identified, and the proteomic model developed shows an excellent discriminatory ability between hypertensives and normotensives. The identified molecular determinants may be the starting point for further studies to clarify the molecular causes of hypertension

High-sensitive Troponin T assay for the diagnosis of acute myocardial infarction: An economic evaluation

__Abstract__ Background: Delayed diagnosis and treatment of Acute Myocardial Infarction (AMI) has a major adverse impact on prognosis in terms of both morbidity and mortality. Since conventional cardiac Troponin assays have a low sensitivity for diagnosing AMI in the first hours after myocardial necrosis, high-sensitive assays have been developed. The aim of this study was to assess the cost effectiveness of a high-sensitive Troponin T assay (hsTnT), alone or combined with the heart-type fatty acid-binding protein (H-FABP) assay in comparison with the conventional cardiac Troponin (cTnT) assay for the diagnosis of AMI in patients presenting to the hospital with chest pain.Methods: We performed a cost-utility analysis (quality adjusted life years-QALYs) and a cost effectiveness analysis (life years gained-LYGs) based on a decision analytic model, using a health care perspective in the Dutch context and a life time time-horizon. The robustness of model predictions was explored using one-way and probabilistic sensitivity analyses.Results: For a life time incremental cost of 30.70 Euros, use of hsTnT over conventional cTnT results in gain of 0.006 Life Years and 0.004 QALY. It should be noted here that hsTnT is a diagnostic intervention which costs only 4.39 Euros/test more than the cTnT test. The ICER generated with the use of hsTnT based diagnostic strategy comparing with the use of a cTnT-based strategy, is 4945 Euros per LYG and 7370 Euros per QALY. The hsTnT strategy has the highest probability of being cost effective at thresholds between 8000 and 20000 Euros per QALY. The combination of hsTnT and h-FABP strategy's probability of being cost effective remains lower than hsTnT at all willingness to pay thresholds.Conclusion: Our analysis suggests that hsTnT assay is a very cost effective diagnostic tool relative to conventional TnT assay. Combination of hsTnT and H-FABP does not offer any additional economic and health benefit over hsTnT test alone

Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice

Objective: Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their clinical use is still lacking. Our aim was to establish if Ang-2 has a role in atheroma development and in the transition of subclinical to clinically relevant atherosclerosis. We investigated the effect of antibody-mediated Ang-2 blockage on atherogenesis after in a mouse model of atherosclerosis. Methods: Hypercholesterolemic (low-density lipoprotein receptor(-/-) apolipoprotein B-100/100) mice were subjected to high-cholesterol diet for eight weeks, one group with and one group without Ang-2 blocking antibody treatment during weeks 4-8. To enhance plaque development, a peri-adventitial collar was placed around the carotid arteries at the start of antibody treatment. Aortic root, carotid arteries and brachiocephalic arteries were analyzed to evaluate the effect of Ang-2 blockage on atherosclerotic plaque size and stable plaque characteristics. Results: Anti-Ang-2 treatment reduced the size of fatty streaks in the brachiocephalic artery (-72%, p <0.05). In addition, antibody-mediated Ang-2 blockage reduced plasma triglycerides (-27%, p <0.05). In contrast, Ang-2 blockage did not have any effect on the size or composition (collagen content, macrophage percentage, adventitial microvessel density) of pre-existing plaques in the aortic root or collar-induced plaques in the carotid artery. Conclusions: Ang-2 blockage was beneficial as it decreased fatty streak formation and plasma triglyceride levels, but had no adverse effect on pre-existing atherosclerosis in hypercholesterolemic mice. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.Peer reviewe