Abstract 458: Role of Colony Stimulating Factor 1 Receptor in Graft Vascular Disease
| Autor: | Vanessa Almonte, Oriyanhan Wunimenghe, Dario F Riascos-Bernal, Prameladevi Chinnasamy, Smitha Jayakumar, Nicholas E Sibinga |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 37 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Heart and kidney transplants are effective treatments for end-stage organ failure, but their long-term success is limited by graft vascular disease (GVD), the leading cause of solid organ transplant failure. This process manifests as concentric thickening of vessel walls due to neointimal hyperplasia in the donor organ, characterized by expansion of cells, notably smooth muscle-like cells (SMLCs) and macrophages (MPs), which accumulate, proliferate, and eventually occlude the lumen of arteries. Our lab recently reported that loss of colony stimulating factor-1 (CSF1) expression in either donor or recipient mice limits GVD, and showed that SMLCs isolated from neointimal lesions express high levels of CSF1 and its receptor, CSF1R. While CSF1-mediated activation of CSF1R has been studied extensively in MP biology, its role in SMLCs and GVD has not been well characterized. We hypothesize that CSF1R activation in neointimal MPs and SMCs occurs after organ transplantation and promotes the development of GVD. To test this idea, carotid arteries from 8-12 week old C57/B6J male mice were transplanted orthotopically into female or male mice. At day 30 post transplantation, sex-mismatched transplants developed significant neointimal lesions not seen in sex-matched controls. Neointimal, adventitial, and to a lesser extent medial cells were positive for CSF1R and CD68, which were scarcely detected in control untransplanted arteries. Cells in the media of transplanted vessels co-stained for smooth muscle alpha actin (SMA) and calponin. SMA-positive cells were found in neointimal lesions, with few cells co-expressing calponin. Proliferation, assessed by Phospho-histone H3 staining, was evident in cells of uncertain origin in the media and neointima. In conclusion, H-Y antigen-driven histoincompatibility in this mouse transplant model yielded vascular lesions that resemble GVD, with significant neointima formation, preservation of medial cells, and evidence of CSF1R expression and of cell proliferation. Future studies will focus on lineage tracing of smooth muscle and myeloid cells to evaluate neointimal cell origins, plus genetic depletion of CSF1R in these cell lineages to determine the requirement for CSF1R expression in the development of GVD. |
| Databáze: | OpenAIRE |
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