Molecular mechanism of aortic dissection : regulation of aortic wall tensile strength through cell-cell interactions

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390334
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Kurume University
• Principal Investigator: AOKI Hiroki 久留米大学, 循環器病研究所, 教授 (60322244)
• Co-Investigator(Kenkyū-buntansha): YOSHIMURA Koichi 山口大学大学院, 医学系研究科, 准教授(特命) (00322248) ; 吉田 恭子 (IMANAKA Kyoko) 三重大学大学院, 医学系研究科, 准教授 (00242967) ; TANAKA Hiroyuki 久留米大学, 医学部, 教授 (70197466)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 大動脈 / 細胞外マトリックス / 炎症 / 細胞間相互作用

Outline of Final Research Achievements

Aortic dissection (AD) is a frequently fatal medical emergency for which molecular pathogenesis is largely unknown. We examined the role of JAK/STAT signaling in macrophages and vascular smooth muscle cells. In human AD tissue, macrophage infiltration was observed in adventitia and outer layer of the media. STAT3 was strongly activated in macrophages and outer layer of the medial smooth muscle cells. In mouse AD model, activation of JAK/STAT in macrophages promoted proinflammatory M1 differentiation and exacerbated AD progression. Activation of JAK/STAT in smooth muscle cells caused proliferation of adventitial fibroblast, deposition of collagen fibers and reinforcement of the tensile strength of aortic walls, thus preventing AD. In AD model, onset of AD was preceded by the activation of cell cycle, inflammatory response and suppression of smooth muscle cell-specific genes. Our findings indicate that JAK/STAT signaling is activated in AD and plays cell type-specific roles.

Free Research Field

分子循環器学