Role of macrophage-derived hypoxia-inducible factor (HIF)-1alpha as a mediator of

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592068
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The University of Tokushima
• Principal Investigator: KINOSHITA Hajime 徳島大学, 大学病院, 特任助教 (80611227)
• Co-Investigator(Kenkyū-buntansha): KITAGAWA Tetsuya 徳島大学, ヘルスバイオサイエンス研究部, 教授 (80240886) ; KITAICHI Takashi 徳島大学, ヘルスバイオサイエンス研究部, 准教授 (20335813) ; SUGANO Mikio 徳島大学, 大学病院, 医員 (70563807) ; NAKAYAMA Taisuke 徳島大学, 大学病院, 医員 (80582791) ; KUROBE Hirotsugu 徳島大学, ヘルスバイオサイエンス研究部, 助教 (30380083) ; FUJIMOTO Eiki 徳島大学, ヘルスバイオサイエンス研究部, 助教 (60611225)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 血管リモデリング / マクロファージ / Hif

Outline of Final Research Achievements

In this study, we clarified the role of macrophage-derived hypoxia-inducible factor (HIF-1α) in vascular remodeling. Wire-induced femoral arterial injury was inflicted in mice lacking the macrophage-specific HIF-1α gene and in their wild-type counterparts. The mutant mice showed both suppressed wire-induced neointimal thickening and decreased infiltration of inflammatory cells in the adventitia, compared to wild-type mice. Studies to clarify the mechanism of restrained vascular remodeling in the mutant mice revealed decreased production of pro-inflammatory cytokines by the activated macrophages and suppressed macrophage migration activity in the mutant mice. Gene expressions of the HIF-1α-deficient macrophages positively correlated with the phenotypic profile of M2 macrophages and negatively correlated with that of M1 macrophages. Our results show that HIF-1α in macrophages plays a crucial role in promoting vascular inflammation and remodeling.

Free Research Field

胸部外科学