Regulation of pathological vascular remodeling by a novel adipocytokines

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09512
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: Ohashi Koji 名古屋大学, 医学系研究科, 寄附講座講師 (10595515)
• Co-Investigator(Kenkyū-buntansha): 大内 乗有 名古屋大学, 医学系研究科, 寄附講座教授 (00595514) ; 室原 豊明 名古屋大学, 医学系研究科, 教授 (90299503)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 血管リモデリング / 抗炎症作用 / 内皮保護作用 / 平滑筋細胞増殖抑制作用

Outline of Final Research Achievements

Dysregulation of adipocytokines are involved in the pathogenesis of vascular disease. We previously identified adipolin (APL) as an insulin-sensitizing adipocytokine reduced in obesity. Here, we investigated whether APL modulates pathological vascular remodeling. APL-knockout (KO) and wild-type (WT) mice were subjected to wire-induced injury of the femoral artery. APL-KO mice showed increased neointimal thickening after vascular injury compared with WT mice, which was accompanied by an enhanced inflammatory response and vascular cell proliferation in injured arteries. Treatment of cultured macrophages with APL reduced inflammatory responses, which were reversed by inhibition of TGFβRII/Smad2 signaling. APL also reduced proliferation of vascular smooth muscle cells (VSMCs) through TGFβ/TGFβRII/Smad2-dependent pathway. Our data indicate that APL protects against the development of pathological vascular remodeling by attenuating macrophage inflammatory responses and VSMC proliferation.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は、肥満でその発現が低下し、インスリン感受性を促進する新規のアディポサイトカインとして、我々が同定したアディポリンに着目し、自ら作製した遺伝子改変マウスを用いて、内因性アディポリンの血管病モデルにおける役割の解明を行うという非常に新規性に富み独創性が高いものである。今回の結果から、内因性のアディポリンの欠如は、肥満に伴う動脈硬化、病的血管リモデリングの増悪に繋がることが示唆され、アディポリンを標的とした研究は、心血管病の病態生理の発見や 新規の治療法の開発に発展する可能性を秘めており、社会的意義も大きい。