Plasmacytoid Dendritic Cells in Atherosclerosis

Atherosclerosis, a chronic inflammatory disease of the vessel wall and the underlying cause of cardiovascular disease, is initiated and maintained by innate and adaptive immunity. Accumulating evidence suggests an important contribution of autoimmune responses to this disease. Plasmacytoid dendritic cells (pDCs), a specialized cell type known to produce large amounts of type I interferons (IFNs) in response to bacterial and viral infections, have recently been revealed to play important roles in atherosclerosis. For example, the development of autoimmune complexes consisting of self-DNA and antimicrobial peptides, which trigger chronic type I IFN production by pDCs, promote early atherosclerotic lesion formation. pDCs and pDC-derived type I IFNs can also induce the maturation of conventional DCs and macrophages, and the development of autoreactive B cells and antibody production. These mechanisms, known to play a role in the pathogenesis of other autoimmune diseases such as systemic lupus erythematosus and psoriasis, may also affect the development and progression of atherosclerotic lesion formation. This review discusses emerging evidence showing a contribution of pDCs in the onset and progression of atherosclerosis

Разработка алгоритмов и программных модулей контроля состояния объекта и аналитической обработки данных в распределенной информационно-телекоммуникационной системе

The following article describes the principles and algorithm for data collection, analytical processing and for monitoring the state of different objects in the distributed information-telecommunication system. As a result it improves the efficiency of the system in general and increases the safety level of citizens during emergency situations

Molecular Imaging of Inflammation in Atherosclerosis

Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic

Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs) and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis

Regulation von Adhäsionsmolekülen und Chemokinen und deren Bedeutung für die entzündliche Monozytenrekrutierung

Die Infiltration mit leukozytären Zellen spielt eine entscheidende Rolle in der Pathogenese glomerulärer Erkrankungen der Niere und wird durch sequentielle und sich überschneidende Interaktionen verschiedener Signalmoleküle gesteuert. In dieser Arbeit wurde die Adhäsionsmolekül- und Chemokinexpression von Mesangialzellen (MC) und glomerulären Endothelzellen (GEC untersucht) und deren Regulation durch verschiedene NF-kappaB Inhibitoren bestimmt. Die Zytokinstimulation der MC mit TNF-alpha induzierte die Transkription und Proteinexpression der Adhäsionsmoleküle ICAM-1 und VCAM-1 sowie der Chemokine GRO-alpha, IL-8, MCP-1, aber nicht Fractalkine. GRO-alpha und IL-8 wurden auf der MC Oberfläche über Heparanproteoglykane immobilisiert, MCP-1 und auch IL-8 als lösliche Moleküle sezerniert. Fractalkine hingegen war nur geringfügig induzierbar konstitutiv auf der MC Oberfläche exprimiert. Diese Induktion der Adhäsionsmoleküle und Chemokine durch Zytokinstimulation der MC war assoziiert mit einer vermehrten Monozytenadhäsion und Transmigration. Dabei vermittelte ICAM-1 und VCAM-1, der GRO-alpha Rezeptor CXCR2 und in geringerem Maße auch Fractalkine den festen monozytären Arrest, während der MCP-1 Rezeptor CCR2 die transendotheliale Chemotaxis von Monozyten auf aktivierte MC zu steuerte. Die transkriptionelle Hochregulation der untersuchten Moleküle wurde über eine Inhibition der IkappaB-alpha Degradation durch den Proteaseninhibitor TLCK, den Proteosomeninhibitor MG132 und durch die adenovirale IkappaB-alpha Überexpression gehemmt. Dies war assoziiert mit der Inhibition der monozytären Adhäsion auf aktivierten MC sowie der transendothelialen Migration auf stimulierte MC zu. Im Gegensatz zu MC wurde Fractalkine auf mRNA wie Proteinebene in transformierten GEC deutlich induziert, und sowohl CXCR2 also auch CX3CR vermittelten den Monozytenarrest auf aktivierten GEC unter Flussbedingungen. Die Relevanz dieser Ergebnisse konnte in einem akzelerierten Glomerulonephritis-Modell an der Ratte bestätigt werden, in dem die Blockade von CCR2 deutlich, und die Blockade von CXCR2 fast komplett die akute glomeruläre Makrophagenrekrutierung inhibierte. Dies unterstreicht die Bedeutung von CXCR2 für die Makrophageninfiltration in den frühen Phasen der NTN. Zusammenfassend erschließt sich ein mehrstufiges Modell, das die inflammatorische Monozytenrekrutierung durch funktionell spezialisierte Adhäsionsmoleküle und Chemokine zeigt

Uranium in the eastern margin of western Siberian plate, or how to overcome crisis of uranium

Теоретические построения [5], свидетельствующие о катагенно-осадочном, эксфильтрационном происхождении железных руд Западно-Сибирского бассейна являются дополнительным фактором принципиальной возможности глубинного происхождения не только радиоактивных металлов, но и ванадия, марганца, благородных металлов и железа. Theoretical constructions [5], which provide evidence of catagenic-aqueous, exfiltration origin of ores of Western Siberian basin, are an additional attribute of principal opportunity for deep seated origin of not only radioactive metals, but also of vanadium, manganese, noble metals and ferrum

Применение метода долгосрочного прогнозирования водонефтяного фактора для определения максимально возможного расчётного объёма добычи нефти месторождения "Чёрный Дракон", Вьетнам

Objective - Although junctional adhesion molecule-A (JAM-A) has recently been implicated in leukocyte recruitment on early atherosclerotic endothelium and after reperfusion injury, its role in neointima formation after arterial injury remains to be elucidated. Methods and Results - Here we show that the genetic deletion of JAM-A in apolipoprotein E - deficient (apoE(-/-)) mice significantly reduced neointimal hyperplasia after wire injury of carotid arteries without altering medial area. This was associated with a significant decrease in neointimal macrophage content, whereas the relative content of smooth muscle cells and endothelial recovery was unaltered in JAM-A(-/-) apoE(-/-) compared with JAM-A(-/-) apoE(-/-) lesions. In carotid arteries perfused ex vivo, deficiency in JAM-A significantly impaired the recruitment of monocytes 1 week, but not 1 day, after injury. These effects were paralleled by an attenuation of monocyte arrest and transmigration on activated JAM-A(-/-) apoE(-/-) versus JAM-A(-/-) apoE(-/-) endothelial cells under flow conditions in vitro. A mechanism underlying reduced recruitment was implied by findings that the luminal expression of the arrest chemokine RANTES in injured arteries and its endothelial deposition by activated platelets in vitro were diminished by JAM-A deficiency. Conclusions - Our data provide the first evidence to our knowledge for a crucial role of JAM-A in accelerated lesion formation and monocyte infiltration in atherosclerosis-prone mice

Problems of methodological determination of the place of financial and budgetary control in the system of state financial control

The relevance of this report due to the presence of problems in the field of budgetary control at all levels of the Russian budget system, which leads to numerous cases of misuse and inefficient use of budget funds and other public property, overestimation of the cost of purchased goods, works and services for state and municipal needs, the use of other corruption schemes in the budget mechanism