3-[(Dodecylthiocarbonyl)Methyl]-Glutarimide Attenuates Graft Arterial Disease by Suppressing Alloimmune Responses and Vascular Smooth Muscle Cell Proliferation
| Autor: | Rumi Igarashi, Satoru Todo, Nozomi Kobayashi, Susumu Shibasaki, Kazuo Umezawa, M. Ogura, Tadashi Yoshida, Moto Fukai, Kenichiro Yamashita, Y. Tsunetoshi, Masaaki Zaitsu |
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| Rok vydání: | 2015 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Vascular smooth muscle endocrine system diseases MAP Kinase Signaling System Arterial disease Myocytes Smooth Muscle Arterial Occlusive Diseases Graft loss Muscle Smooth Vascular Organ transplantation Interferon-gamma Mice 3-((dodecylthiocarbonyl)methyl)glutarimide Transplant organ Isoantibodies Animals Transplantation Homologous Medicine Cells Cultured Piperidones Transplantation business.industry Cell growth Histocompatibility Testing nutritional and metabolic diseases Mice Inbred C57BL surgical procedures operative Immunology Heart Transplantation business |
| Zdroj: | Transplantation. 99:948-956 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0000000000000576 |
| Popis: | Graft arterial disease (GAD) is a major cause of late graft loss after organ transplantation. Alloimmune responses and vascular remodeling eventually cause the transplant organ to develop GAD. In this study, we aimed to limit the development of GAD by inhibiting alloimmune responses and vascular smooth muscle cell (VSMC) proliferation with a new compound, 3-[(dodecylthiocarbonyl)methyl]-glutarimide ([DTCM]-glutarimide), in a murine cardiac model of GAD.The hearts from B6.CH-2 mice were transplanted into C57BL/6 mouse recipients to examine the extent of GAD. The recipients were treated with either vehicle or DTCM-glutarimide intraperitoneally (40 mg/kg per day) for 4 weeks.The administration of DTCM-glutarimide attenuated GAD formation (luminal occlusion: 37.9 ± 5.9% vs 14.8 ± 5.4%, P0.05) by inhibiting the number of graft-infiltrating cells and decreasing alloreactive interferon (IFN)-γ production compared with control mice, as measured by the Enzyme-linked ImmunoSpot assay. In vitro, VSMCs proliferated on stimulation with either basic fibroblast growth factor or IFN-γ and splenocytes after transplantation, but the addition of DTCM-glutarimide resulted in the inhibition of VSMC proliferation. Moreover, DTCM-glutarimide suppressed cyclin D1 expression and inhibited cell cycle progression from G1 to S in VSMCs.The compound DTCM-glutarimide suppressed GAD development by inhibiting not only alloimmune responses but also VSMC proliferation in the graft. |
| Databáze: | OpenAIRE |
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