Rôle de l’immunité dans l’athérosclérose et dans les syndromes coronariens aigus Role of the immune response in atherosclerosis and acute coronary syndromes

Résumé

La formation et le développement des plaques d’athérome résultent d’une interaction dynamique entre la paroi des vaisseaux et le sang circulant. L’étape cruciale de la constitution des plaques semble être la présence de lipoprotéines oxydées dans l’espace sous-endothélial, qui entraîne l’expression locale de facteurs responsables de l’infiltration de la paroi par des monocytes et des lymphocytes T. L’athérosclérose est ainsi une maladie immuno-inflammatoire, différents composants du système immunitaire assumant un rôle protecteur ou délétère dans le devenir de la maladie. D’où l’idée de développer, à partir de la modulation de la réponse immunitaire, de nouvelles thérapeutiques préventives et curatives pour lutter contre les maladies cardiovasculaires, première cause de décès dans les pays industrialisés.

Summary

Cardiovascular diseases represent one of the most important causes of death in the world. The underlying pathogenetic process is atherosclerosis which leads to the progressive reduction of the arterial lumen and therefore to the ischemia of the perfused organs. Atherogenesis results from the interaction between the biology of the arterial wall and the various stress stimuli present in the circulating blood. The first steps of atherogenesis occur very early, already during the fetal life. Those arterial segments that are subjected to the initiating causes (including hemodynamic stress) show altered endothelial permeability and allow the infiltration of macromolecules, like lipoproteins, in the subintimal space. At the same time, the smooth muscle cells that are subjected to the same local factors produce proteoglycans able to bind lipoproteins and to promote their oxidation. Oxidized lipoproteins induce the expression of chemokines and adhesion molecules on the luminal surface of the endothelium, which then allow the local recruitment of monocytes-macrophages and T lymphocytes. This is a local inflammatory process that, in theory, should contribute to reestablish the homeostasis of the vascular wall by promoting the elimination of injured tissue and its repair. Unfortunately, for unknown reasons, the immuno-inflammatory reaction persists and autoamplifies, the various components of the immune response finally contributing to the pathogenesis of atherosclerosis as well as of atherosclerotic complications.