Aim: Tumor necrosis factor receptor 1 (TNFR1) participates importantly in arterial inflammation in genetically altered mice; however it remains undetermined whether a selective TNFR1 antagonist inhibits arterial inflammation and intimal hyperplasia. This study aimed to determine the effect and mechanism of a novel TNFR1 antagonist in the suppression of arterial inflammation. Methods: We investigated intimal hyperplasia in IL-1 receptor antagonist-deficient mice two weeks after inducing femoral

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... rtery injury in an external vascular cuff model. All mice received intraperitoneal injections of TNFR1 antagonist (PEG-R1antTNF) or normal saline twice daily for 14 days. Results: PEG-R1antTNF treatment yielded no adverse systemic effects, and we observed no significant differences in serum cholesterol or blood pressure in either group; however, selective PEG-R1antTNF treatment significantly reduced intimal hyperplasia (19,671 4,274 vs. 11,440 3,292 m 2 ; p 0.001) and the intima/media ratio (1.86 0.43 vs. 1.34 0.36; p 0. 029), compared with saline injection. Immunostaining revealed that PEG-R1antTNF inhibits Nuclear factor-B (NF-B), suppressing smooth muscle cell (SMC) proliferation and decreasing chemokine and adhesion molecule expression, and thus decreasing intimal hyperplasia and inflammation. Conclusions: Our data suggest that PEG-R1antTNF suppresses SMC proliferation and inflammation by inhibiting NF-B. This study highlights the potential therapeutic benefit of selective TNFR1 antagonist therapy in preventing intimal hyperplasia and arterial inflammation.