The aim of this study was to explore the use of urantide as an antagonist of the urotensin II (UII) receptor, G protein-coupled receptor 14 (GPR14), to protect against atherosclerosis (AS) in rats. The AS rat model was induced by an intraperitoneal injection of vitamin D3 (VD3) into rats fed with a high-fat diet for four weeks. Urantide was then injected into the rats. Immunohistochemical staining, serum biochemical assay, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to investigate the expression of UII and its receptor GPR14 in the AS rat model. Four weeks after induction, pathological changes typical of AS were observed in the AS rat model. In the plaques of the aortic tunica intima and tunica media, expression of UII and GPR14 was observed. The protein and gene expression levels of UII and GPR14 in the model group were significantly increased compared with those in the normal group (P<0.01). Urantide ameliorated the pathological changes of AS in the rat model and reduced the gene and protein expression levels of UII and GPR14 (P<0.05 or P<0.01). UII is associated with AS and the UII receptor GPR14-specific antagonist, urantide, demonstrates the ability to protect against AS. Thus, this study provides new insight and experimental theories for the clinical application of urantide to treat AS.

The aim of the present study was to investigate the effects of urantide on the expression status of C-reactive protein (CRP) and the inflammatory cytokines monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-β in the aortas of rats with atherosclerosis (AS), and to identify its underlying mechanisms. The effects of urantide in a rat model of AS and in cultured rat vascular smooth muscle cells (VSMCs) were analyzed via hematoxylin and eosin staining, immunohistochemical staining and ELISA. The results in vivo demonstrated that urantide downregulated the expression of inflammatory mediators CRP and MCP-1 and upregulated the expression of TGF-β. The results in vitro indicated that urantide inhibited the proliferation of VSMCs. In addition, urantide reduced the expression of CRP and downregulated the secretion of TGF-β in the culture supernatant. In conclusion, urantide ameliorated the arterial inflammatory damage that was observed in the AS rat model at the cell and tissue levels by controlling the expression of CRP and the inflammatory cytokines MCP-1 and TGF-β. Therefore, urantide may be a potential agent for the complementary treatment of AS.