Macrophage Death as a Pharmacological Target in Atherosclerosis

Atherosclerosis is a chronic inflammatory disorder characterized by the gradual build-up of plaques within the vessel wall of middle-sized and large arteries. Over the past decades, treatment of atherosclerosis mainly focused on lowering lipid levels, which can be accomplished by the use of statins. However, some patients do not respond sufficiently to statin therapy and therefore still have a residual cardiovascular risk. This issue highlights the need for novel therapeutic strategies. As macrophages are implicated in all stages of atherosclerotic lesion development, they represent an important alternative drug target. A variety of anti-inflammatory strategies have recently emerged to treat or prevent atherosclerosis. Here, we review the canonical mechanisms of macrophage death and their impact on atherogenesis and plaque stability. Macrophage death is a prominent feature of advanced plaques and is a major contributor to necrotic core formation and plaque destabilization. Mechanisms of macrophage death in atherosclerosis include apoptosis, passive or accidental necrosis as well as secondary necrosis, a type of death that typically occurs when apoptotic cells are insufficiently cleared by neighboring cells via a phagocytic process termed efferocytosis. In addition, less-well characterized types of regulated necrosis in macrophages such as necroptosis, pyroptosis, ferroptosis, and parthanatos may occur in advanced plaques and are also discussed. Autophagy in plaque macrophages is an important survival pathway that protects against cell death, yet massive stimulation of autophagy promotes another type of death, usually referred to as autosis. Multiple lines of evidence indicate that a better insight into the different mechanisms of macrophage death, and how they mutually interact, will provide novel pharmacological strategies to resolve atherosclerosis and stabilize vulnerable, rupture-prone plaques

Le bien-être des élèves en établissement scolaire Zoom sur les élèves en classe de sixième

The well-being of students at school is a recurring problem for the CPE. (Principal Educational Adviser) The COVID crisis and lockdowns have disrupted the fragile balance of adolescents, with an impact on schools. Our research internship on "Health and well-being in school and university paths" gave us the opportunity to observe and participate in the development of the "Welln'ESS" project. Then our internship observations naturally have us to work on well-being and health at school. The notion of well-being refers in the common sense to a set of factors considered separately or jointly: health, social or economic success, pleasure, self-realization. Well-being, whether physical or psychological, can be defined as a pleasant but transient state, provided by the satisfaction of the body's needs and by the peace of mind, free of the famous "stress". Well-being is part of health, at least in the definition given by the WHO. Well-being, for students, corresponds to a set of elements such as health, satisfaction of these needs, pleasure, self-realization, harmony with oneself and with others that provides peace of mind. It is a pleasant but not permanent condition. Unlike health, which is a data that can be objective, well-being is purely subjective: well-being or ill-being, it is felt, is eventually told, but it is not evaluated, not measured, not transmitted either. After taking stock of research, we propose a practice in our internship fields: a questionnaire to 6ième students and the establishment of workshops to strengthen psycho-social skills.Le bien-être des élèves à l’école est une problématique récurrente du CPE.La crise du COVID et les confinements ont perturbés l’équilibre fragile des adolescents, avec un impact dans les établissements scolaires.Notre stage de recherche portant sur la « Santé et bien-être dans les parcours scolaire et universitaire », nous a offert l’occasion d’observer et de participer à l’élaboration du projet « Welln’ESS ».Puis nos observations de stage nous ont naturellement amené à travailler sur le bien-être et la santé à l’école.La notion de bien-être renvoie dans le sens commun à un ensemble de facteurs considérés de façon séparée ou conjointe : la santé, la réussite sociale ou économique, le plaisir, la réalisation de soi.Le bien-être, qu’il soit physique ou psychique, peut être défini comme un état agréable mais transitoire, procuré par la satisfaction des besoins du corps et par la tranquillité de l’esprit, débarrassé du fameux « stress ». Le bien-être fait partie de la santé, du moins dans la définition qu’en donne l’OMS.Le bien-être, pour les élèves, correspond à un ensemble d’éléments tels que la santé, la satisfaction de ces besoins, le plaisir, la réalisation de soi, l’harmonie avec soi-même et avec les autres qui procure la tranquillité de l’esprit. Il est un état agréable mais non pérenne.Contrairement à la santé, qui est une donnée que l’on peut objectiver, le bien-être est purement subjectif : le bien-être ou le mal-être, cela se ressent, se raconte éventuellement, mais cela ne s’évalue pas, ne se mesure pas, ne se transmet pas non plus.Après avoir fait un état des lieux de la recherche, nous proposons une mise en pratique dans nos terrains de stage : une passation de questionnaire aux élèves de 6ième et la mise en place d’ateliers de renforcement des compétences psycho sociales

Cellular expression of A20 and ABIN-3 in response to Toll-like receptor-4 stimulation

Although Toll-like receptor (TLR)-induced expression of several proinflammatory genes is required to provoke an efficient immune response, excessive or prolonged activation of TLR signaling can contribute to the development of septic shock and several inflammatory diseases. Given this inherent danger of unrestrained TLR signaling to the organism, it is not surprising that many negative feedback mechanisms have evolved to hold TLR signaling in check. In this context, TLR stimulation induces several negative regulators of TLR-induced signaling to nuclear factor (NF)-kappaB dependent gene expression. Here we describe the use of Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) to study respectively the cellular protein and mRNA expression levels of the NF-kappaB inhibitory proteins A20 and ABIN-3 in response to TLR4 stimulation by lipopolysaccharide (LPS)