Novel therapeutic strategy for aortic aneurysm targeting master cytokine and cellular senescence

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Abdominal aortic aneurysm(AAA) is common to eldery people, of which molecula pathogenesis is largely unknown. We hypothesized that IL-6 may be the master cytokine for regulating the chronic inflammation and tissue destruction in AAA. Indeed, IL-6 was one of the most abundantly expressed cytokines and regulating a subset of proinflammatory cytokines, including VEGF and MCP-3, in human AAA tissue. In mouse model of AAA, IL-6 expression was associated with the expansion of aortic diameter, and was involved in the progression of AAA. Although macrophages are important in pathogenesis of AAA, enhanced IL-6 signaling in macrophages did not affect AAA development. Thus, IL-6-dependent development of AAA appeared to be mediated by cell types other than macrophages. Unexpectedly, we discovered that macrophage IL-6 signaling was critically involved in the development of acute aortic dissection. In the future studies, we will address which cell type is responsible for the IL-6-dependent devopment of AAA, and how macrophage IL-6 is involved in the pathogenesis of aortic dissection.