Abstract 412: Radio Protective P105 Deficiency Aggravates Vein Graft Disease And Lesion Instability via Increased Inflammatory Responses
| Autor: | Margreet R de Vries, Anouk Wezel, Erna H Peters, Jacco C Karper, Johan Kuiper, Ilze Bot, Paul H Quax |
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| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 35 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvb.35.suppl_1.412 |
| Popis: | Aim: Vein grafts are often used to bypass atherosclerotic lesions; however, patency rates are troublesome due to the development of vein graft disease. Deficiency of toll like receptor (TLR)4, a key initiator of inflammatory signaling, results in reduced vein graft disease. As TLR4 signaling is regulated by the accessory molecule RadioProtective 105 (RP105), we aimed to investigate the effects of RP105 on vein graft disease. Methods and results: Vein graft surgery was performed on Rp105-/- mice (n=13) and C57BL/6 mice (n=11), as well as on LDLr-/-/Rp105-/- mice (n=11) and LDLr-/- mice (n=11) fed a western type diet, 28 days later lesion size and composition was analysed. A 90% increase in vein graft lesion size was observed in RP105-/- mice compared to controls. Lesion size however, did not differ between LDLr-/-/RP105-/- mice and LDLr-/- mice, but interestingly, a significant increase in the number of unstable lesions and intraplaque hemorrhage upon RP105 deficiency was observed. In both experimental setups, an increase in lesional macrophages was seen. Peritoneal Rp105-/- macrophages showed an increase in proliferation. Whereas, Rp105-/-smooth muscle cells and bone marrow derived mast cells secreted increased levels of the monocyte chemoattractant CCL2. In both the Rp105-/- and LDLr-/-/Rp105-/- vein grafts the amount of lesional CCL2 was significantly increased, as well as the number of activated perivascular mast cells. Conclusions: Together, these data indicate that RP105 has a protective role in vein graft disease by dampening the inflammatory effect, since RP105 deficiency results in an increased inflammatory response and exacerbated CCL2 production by both mast cells and smooth muscle cells. |
| Databáze: | OpenAIRE |
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