NLRC5 inhibits neointima formation following vascular injury and directly interacts with PPARγ

• Published in: Nature communications Vol. 10; no. 1; pp. 2882 - 16
• Main Authors: Luan, Peipei, Jian, Weixia, Xu, Xu, Kou, Wenxin, Yu, Qing, Hu, Handan, Li, Dali, Wang, Wei, Feinberg, Mark W., Zhuang, Jianhui, Xu, Yawei, Peng, Wenhui
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.06.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/31; 13/51; 13/89; 13/95; 14; 14/34; 49/109; 631/443/592/75/593; 631/80/86/388; 64/60; Animals; Antigen presentation; Antigens; Aorta; Apoptosis; Blood Pressure; Bone Marrow Transplantation; Cell Proliferation; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Heart Rate; Humanities and Social Sciences; Humans; Hyperplasia; Immunity; Innate immunity; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Knockout; multidisciplinary; Muscles; Myocytes, Smooth Muscle - metabolism; Pioglitazone; Plasmids; Rodents; Science; Science (multidisciplinary); Smooth muscle; Transcriptome; Tunica Intima - metabolism; Vascular Remodeling
• ISSN: 2041-1723; 2041-1723
• 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. NLRC5 is known for its role in inflammation and antigen presentation. Here Luan et al. find that NLRC5 protects mice from intimal hyperplasia following vascular injury, and regulates the response of vascular smooth muscle cells to injury through direct interaction with PPARγ.