STAT3, A Double-edged Sword in Pathogenesis of Aortic Dissection

Abstract

Aortic dissection (AD) is an acute and fatal aortic disease for which pathogenesis is largely unknown. While recent studies have highlighted the importance of IL-6 signaling that governs the destructive inflammatory response involving neutrophils and macrophages, precise disease mechanism remains to be elucidated. We examined the activation of STAT3, a signaling molecule that mediate the function of IL-6, in human AD tissue. STAT3 was activated in infiltrating macrophages and in medial smooth muscle cells. Tissue-specific deletion of SOCS3 gene, a negative regulator of STAT3, was utilized to enhance the STAT3 sensitivity in macrophages or in smooth muscle cells. STAT3 activation in macrophage resulted exaggerated AD by enhancing tissue destructive inflammation in mouse aorta. In contrast, STAT3 activation in smooth muscle cells ameliorated AD by collagen deposition and reinforcement of adventitia. These results indicate the presence of complex intercellular network in AD pathogenesis, of which clarification would lead to the development of better clinical strategies.