Ying and Yang of Stat3 in pathogenesis of aortic dissection

Aortic dissection (AD) is a medical emergency, in which acute destruction of aortic wall occurs with unknown etiology. Recent studies have uncovered the critical role inteleukin-6 (IL-6) and inflammatory cells including macrophages disease mechanism AD. IL-6 activates janus kinase signal transducer activator transcription 3 (STAT3) to alter gene expression program many cell types, thus regulating various aspects response. We found that human AD tissue, STAT3 was activated infiltrating medial smooth muscle (SMCs), suggesting may regulate response these types. However, it how Stat3 regulates type-specific pathogenesis The examined genetically modified mice sensitivity enhanced specifically or SMCs by tissue-specific deletion suppressor cytokine signaling (Socs3), negative regulator STAT3. Macrophage-specific Socs3 caused enhancement activation, M1-dominant differentiation macrophages, suppression tissue repair SMCs, exaggerated In contrast, SMC-specific chronic activation low-grade walls, fibroblasts, M2-dominant increase adventitial collagen deposition, resulting protection aorta from reinforcing tensile strength walls. Therefore, balance between reinforcement depending on types time course ultimately development Elucidating such dynamic integrity would be essential decipher molecular