epartment of Cardiovascular Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):210-7. doi: 10.1161/ATVBAHA.109.192666. Epub 2009 Dec 10.
Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis.
To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice.
The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.
最近的研究表明，细胞免疫反应在血管重构的发展中调节所导致的病理改变。我们表明，缺氧诱导因子 1（Hif-1）（特异性表达于 T 细胞）参与伴随动脉粥样硬化的血管重构的免疫反应。
为了研究 T 细胞在血管重构发展中的作用，在外周血管聚乙烯套管引起的股动脉损伤的情况下，在缺乏 Hif-1（特异性表达于 T 细胞）的小鼠中检查了血管重构。我们发现，与对照小鼠相比，套管放置导致 Hif-1-（T 细胞）缺陷小鼠的股动脉显著的新生内膜增生，并且在突变小鼠中，外膜的炎性细胞浸润明显增加。阐明突变小鼠中增强的血管重构的机制的研究表明，激活的 T 细胞产生细胞因子增加，并且对 T 依赖性抗原的抗体产生增加。
本研究的结果表明，T 细胞中的 Hif-1alpha 作为 T 细胞介导的免疫反应的负调节剂，在套管损伤引起的血管炎症和重构中发挥关键作用。描述了针对 Hif-1alpha 的潜在新的治疗策略。
