Читать книгу Interventional Cardiology - Группа авторов - Страница 25

Immunoinflammation drives the formation, progression, and rupture of atherosclerotic plaques. Early phases of the plaque development are characterized by an acute innate immune response against exogenous (infectious) and endogenous non‐infectious stimuli. Specific antigens activate adaptive immune system leading to proliferation of T and B cells. A first burst of activation might occur in regional lymph nodes by dendritic cells (DCs) trafficking from the plaque to lymph node. Subsequent cycle of activation can be sustained by interaction of activated /memory T cells re‐entering in the plaque by selective binding to endothelial cell surface adhesion molecules with plaque macrophages expressing MHC class II molecules. In this phase of the atherogenic process the selective recruitment of a specific subtype of CD4+ cells play a major role determining the future development of the lesion. Th1 cells secreting proiflammatory cytokines, such as IFNγ promote macrophage activation, inflammation, and atherosclerosis, whereas Th2 cells (cytokine pattern IL‐4, IL‐5 and IL‐10) mediate antibody production and generally have anti‐inflammatory and antiatherogenic effects [92]. Therefore, the switch to a selective recruitment of Th1 lymphocyte represents a key point toward plaque vulnerability/disruption. T cells in the plaque may encounter antigens such as oxLDL. Moreover T cell response can be triggered by heat shock proteins of endogenous or microbial origins [93]. The mechanisms of why the initial inflammatory response becomes a chronic inflammatory condition remains unclear. However, when the plaque microenvironment triggers the selective recruitment and activation of Th1 cells they in turn determine a potent inflammatory cascade.

The combination of IFNγ and TNFα upregulates the expression of fractalkine (CX3CL1) [94]. Interleukin 1 and TNFα‐activated endothelium express also fractalkine (membrane bound form) that directly mediates the capture and adhesion of CX3CR1 expressing leukocytes providing a further pathway for leukocyte activation [95]. This cytokine network promotes the development of the Th‐1 pathway which is strongly pro‐inflammatory and induces macrophage activation, superoxide production and protease activity.