NLRC5 抑制血管损伤后的新内膜形成，并与 PPARγ 直接相互作用。
NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ.
机构信息
Department of Cardiology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200092, China.
出版信息
Nat Commun. 2019 Jun 28;10(1):2882. doi: 10.1038/s41467-019-10784-y.
NLR Family CARD Domain Containing 5 (NLRC5), an important immune regulator in innate immunity, is involved in regulating inflammation and antigen presentation. However, the role of NLRC5 in vascular remodeling remains unknown. Here we report the role of NLRC5 on vascular remodeling and provide a better understanding of its underlying mechanism. Nlrc5 knockout (Nlrc5) mice exhibit more severe intimal hyperplasia compared with wild-type mice after carotid ligation. Ex vivo data shows that NLRC5 deficiency leads to increased proliferation and migration of human aortic smooth muscle cells (HASMCs). NLRC5 binds to PPARγ and inhibits HASMC dedifferentiation. NACHT domain of NLRC5 is essential for the interaction with PPARγ and stimulation of PPARγ activity. Pioglitazone significantly rescues excessive intimal hyperplasia in Nlrc5 mice and attenuates the increased proliferation and dedifferentiation in NLRC5-deficient HASMCs. Our study demonstrates that NLRC5 regulates vascular remodeling by directly inhibiting SMC dysfunction via its interaction with PPARγ.
NLR 家族 CARD 结构域包含 5（NLRC5），是先天免疫中重要的免疫调节剂，参与调节炎症和抗原呈递。然而，NLRC5 在血管重构中的作用尚不清楚。在这里，我们报告了 NLRC5 在血管重构中的作用，并提供了对其潜在机制的更好理解。NLRC5 敲除（Nlrc5）小鼠与野生型小鼠相比，在颈动脉结扎后表现出更严重的内膜增生。离体数据表明，NLRC5 缺失导致人主动脉平滑肌细胞（HASMC）的增殖和迁移增加。NLRC5 与 PPARγ 结合并抑制 HASMC 去分化。NLRC5 的 NACHT 结构域对于与 PPARγ 的相互作用和刺激 PPARγ 活性是必不可少的。吡格列酮可显著挽救 Nlrc5 小鼠中过度的内膜增生，并减轻 NLRC5 缺陷型 HASMC 中增殖和去分化的增加。我们的研究表明，NLRC5 通过其与 PPARγ 的相互作用直接抑制 SMC 功能障碍来调节血管重构。
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