Open AccessInterferon Regulatory Factor 7 Protects Against Vascular Smooth Muscle Cell Proliferation and Neointima Formation
Author(s) -
Huang Ling,
Zhang ShuMin,
Zhang Peng,
Zhang XiaoJing,
Zhu LiHua,
Chen Ke,
Gao Lu,
Zhang Yan,
Kong XiangJie,
Tian Song,
Zhang XiaoDong,
Li Hongliang
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.114.001309
Subject(s) - medicine , neointima , vascular smooth muscle , cell growth , microbiology and biotechnology , interferon , smooth muscle , cancer research , immunology , biochemistry , restenosis , stent , biology , chemistry
Background Interferon regulatory factor 7 ( IRF 7), a member of the interferon regulatory factor family, plays important roles in innate immunity and immune cell differentiation. However, the role of IRF 7 in neointima formation is currently unknown. Methods and Results Significant decreases in IRF 7 expression were observed in vascular smooth muscle cells ( VSMC s) following carotid artery injury in vivo and platelet‐derived growth factor‐ BB ( PDGF ‐ BB ) stimulation in vitro. Compared with non‐transgenic ( NTG ) controls, SMC ‐specific IRF 7 transgenic ( IRF 7‐ TG ) mice displayed reduced neointima formation and VSMC proliferation in response to carotid injury, whereas a global knockout of IRF 7 ( IRF 7‐ KO ) resulted in the opposite effect. Notably, a novel IRF 7‐ KO rat strain was successfully generated and used to further confirm the effects of IRF 7 deletion on the acceleration of intimal hyperplasia based on a balloon injury‐induced vascular lesion model. Mechanistically, IRF 7's inhibition of carotid thickening and the expression of VSMC proliferation markers was dependent on the interaction of IRF 7 with activating transcription factor 3 ( ATF 3) and its downstream target, proliferating cell nuclear antigen ( PCNA ). The evidence that IRF 7/ ATF 3‐double‐ TG ( DTG ) and IRF 7/ ATF 3‐double‐ KO ( DKO ) mice abolished the regulatory effects exhibited by the IRF 7‐ TG and IRF 7‐ KO mice, respectively, validated the underlying molecular events of IRF 7‐ ATF 3 interaction. Conclusions These findings demonstrated that IRF 7 modulated VSMC proliferation and neointima formation by interacting with ATF 3, thereby inhibiting the ATF 3‐mediated induction of PCNA transcription. The results of this study indicate that IRF 7 is a novel modulator of neointima formation and VSMC proliferation and may represent a promising target for vascular disease therapy.