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Les évènements cardiovasculaires sont la première cause de mortalité chez les patients insuffisants rénaux chroniques. Ces complications font suite à des modifications structurelles et fonctionnelles de la paroi vasculaire regroupées sous le terme de vasculopathie urémique. Parallèlement à ces modifications vasculaires, l’urémie s’accompagne d’une accumulation de substances non épurées par le rein appelées toxines urémiques, telles que les produits de la glycation avancée (AGEs) ou les ligands de RAGE. Ces toxines peuvent interagir avec leur récepteur, RAGE, qui est pro- inflammatoire et impliqué dans le remodelage artériel. Cette thèse a consisté en l’étude, chez la souris, du rôle de l’accumulation des ligands de RAGE et de leur interaction avec celui-ci dans le développement de l’athérosclérose, des calcifications vasculaires et de la thrombose artérielle au cours de l’insuffisance rénale chronique (IRC). Dans un premier temps, nous avons montré que l’IRC conduisait à une accumulation des AGEs et des ligands de RAGE sériques et tissulaires, ainsi qu’une augmentation de l’expression de RAGE au sein de la paroi vasculaire participant à la formation des plaques d’athérome. Dans un second temps, nous avons démontré que RAGE participait aux calcifications vasculaires favorisant l’expression de co-transporteur de phosphate inorganique (Pit-1), induisant la différenciation des cellules musculaires lisses en cellules « osteoblast-like ». Enfin, nous avons montré que RAGE participait à la formation d’un thrombus artériel dû à une hyperactivité plaquettaire. En conclusion, cette thèse a permis de renforcer le concept que l’axe ligands de RAGE/RAGE est un acteur important dans la vasculopathie urémique. / Cardiovascular events are the primary cause of morbidity and mortality in chronic kidney disease patients. These complications are due to structural and functional changes in the vascular wall named uraemic vasculopathy. Alongside these vascular changes, uremia is accompanied by the retention of various solutes that are normally excreted by the kidneys called uremic toxins, such as the products of advanced glycation (AGEs) or the ligands of RAGE. These toxins may interact with their receptor, RAGE, which is pro-inflammatory and involved in arterial remodeling. The aim of this thesis was to study, in mice, the role of the accumulation of RAGE ligands and their interaction with it in the development of atherosclerosis, vascular calcification and arterial thrombosis in chronic renal failure (CKD). Initially, we showed that CKD leads to an accumulation of serum and tissue AGEs and RAGE ligands, as well as an increase in RAGE expression in the vascular wall involved in atheroma plaque formation. Secondly, we have demonstrated that RAGE is involved in vascular calcification promoting the expression of inorganic phosphate cotransporter (Pit-1), inducing the differentiation of smooth muscle cells "osteoblast-like". Finally, we showed that RAGE participated in the formation of arterial thrombus due to platelet hyperactivity. In conclusion this thesis consolidates that RAGE-RAGE ligands axis is an important actor in uremic vasculopathy.

This study contributes to the ongoing debate about the existence and nature of the Cathar heresy in Languedoc in the long thirteenth century. Using testimony of accused heretics, it traces a network of fundraising, donations, testamentary bequests, deposit-holding, moneylending, and other types of financial transactions that evidences the existence of a discreet group of people traditionally called ‘Cathars’. This study demonstrates that, unlike many other medieval religious movements, this group did not practice voluntary poverty as part of a holy life. Since the Cathars are traditionally thought to be radical dualists who rejected the material world in all its forms, and because their clergy professed asceticism in other aspects of life, the failure to embrace holy poverty struck contemporary observers as hypocritical and self-serving. Many modern historians have agreed with this assessment, while others have argued that the Cathars did, in fact, embrace poverty. This study serves as a corrective to both points of view: the ‘Cathars’ in thirteenth-century Languedoc neither embraced poverty, nor cynically claimed to do so while disregarding their principles. Rather, repudiation of money was not part of their way of life. That the Cathars of Languedoc did not embrace apostolic poverty is not surprising when we consider that they were embedded in a local culture with strong moneylending traditions. These local practices did not conform to the norms of the Catholic church, rendering the region vulnerable to charges of usury as well as heresy. As part of its effort to standardize religious practice, in the thirteenth century the papacy waged an aggressive campaign against Cathar heresy. Uneasy with the rapid economic expansion of the high Middle Ages, it also stepped up attacks on usury, which was seen by some as a kind of heresy. Seeing that Cathars did not embrace holy poverty – and, in fact, participated in the economy – contemporary critics accused them of practicing usury and pursuing wealth. Languedoc, already deeply associated with Catharism, came under attack in the thirteenth century for its credit culture as well. Using case studies of early thirteenth-century Toulouse and late thirteenth-century Albi, this dissertation examines the association between heresy and usury and argues that attacks on their practitioners were intended to enforce conformity to orthodox norms and eradicate difference within Latin Christendom.

Thesis (Ph. D.)--Catholic University of America, 1934. / Bibliography: p. 159-163.

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Contemporary pilgrimage activities associated with the Volto Santo may be traced to the origins of the cult, which, as I argue in this dissertation, was established in the late eleventh century. I propose this new date of the cult's establishment, as well as its development and promotion in the twelfth and thirteenth centuries, based on research in the areas of Lucca's political, religious, and economic histories, as well as other Lucchese relic cults, the hagiographic and iconographic traditions associated with the Volto Santo, other competing relic cults in Tuscany, and the impact of Lucca's textile industry. This dissertation provides the first substantial contribution to the art historical contextualization of Il Volto Santo during the latter Middle Ages by investigating the intricate relationships between the religious, political, and economic affairs involving the Volto Santo during the late eleventh through thirteenth centuries. In addition, it complements the growing scholarship dedicated to pilgrimage studies associated with the Via Francigena. / A Dissertation submitted to the Department of Art History in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Fall Semester 2015. / October 29, 2015. / Includes bibliographical references. / Paula L. Gerson, Professor Directing Dissertation; Irene Zanini-Cordi, University Representative; Lynn Jones, Committee Member; Stephanie Leitch, Committee Member.