Interferon regulatory factor 7 protects against vascular smooth muscle cell proliferation and neointima formation

Background-interferon regulatory factor 7 (irf7),a member of the interferon regulatory factor family,plays important roles in innate immunity and immune cell differentiation. however,the role of irf7 in neointima formation is currently unknown. methods and results-significant decreases in irf7 expression were observed in vascular smooth muscle cells (vsmcs) 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 irf7 transgenic (irf7-tg) mice displayed reduced neointima formation and vsmc proliferation in response to carotid injury,whereas a global knockout of irf7 (irf7-ko) resulted in the opposite effect. notably,a novel irf7-ko rat strain was successfully generated and used to further confirm the effects of irf7 deletion on the acceleration of intimal hyperplasia based on a balloon injury-induced vascular lesion model. mechanistically,irf7's inhibition of carotid thickening and the expression of vsmc proliferation markers was dependent on the interaction of irf7 with activating transcription factor 3 (atf3) and its downstream target,proliferating cell nuclear antigen (pcna). the evidence that irf7/atf3-double-tg (dtg) and irf7/atf3-double-ko (dko) mice abolished the regulatory effects exhibited by the irf7-tg and irf7-ko mice,respectively,validated the underlying molecular events of irf7-atf3 interaction. conclusions-these findings demonstrated that irf7 modulated vsmc proliferation and neointima formation by interacting with atf3,thereby inhibiting the atf3-mediated induction of pcna transcription. the results of this study indicate that irf7 is a novel modulator of neointima formation and vsmc proliferation and may represent a promising target for vascular disease therapy. © 2014 the authors.