Peroxisome Proliferator-Activated Receptor-gamma Agonists Prevent In Vivo Remodeling of Human Artery Induced by Alloreactive T Cellsopen access
- Authors
- Tobiasova, Zuzana; Zhang, Lufeng; Yi, Tai; Qin, Linfeng; Manes, Thomas D.; Kulkarni, Sanjay; Lorber, Marc I.; Rodriguez, Frederick C.; Choi, Je-Min; Tellides, George; Pober, Jordan S.; Kawikova, Ivana; Bothwell, Alfred L. M.
- Issue Date
- Jul-2011
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Keywords
- arteriosclerosis; mice; PPAR gamma; T-lymphocytes; vascular diseases
- Citation
- CIRCULATION, v.124, no.2, pp.196 - U199
- Indexed
- SCIE
SCOPUS
- Journal Title
- CIRCULATION
- Volume
- 124
- Number
- 2
- Start Page
- 196
- End Page
- U199
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/168091
- DOI
- 10.1161/CIRCULATIONAHA.110.015396
- ISSN
- 0009-7322
- Abstract
- Background-Ligands activating the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR gamma) have antiinflammatory effects. Vascular rejection induced by allogeneic T cells can be responsible for acute and chronic graft loss. Studies in rodents suggest that PPAR gamma agonists may inhibit graft vascular rejection, but human T-cell responses to allogeneic vascular cells differ from those in rodents, and the effects of PPAR gamma in human transplantation are unknown. Methods and Results-We tested the effects of PPAR gamma agonists on human vascular graft rejection using a model in which human artery is interposed into the abdominal aorta of immunodeficient mice, followed by adoptive transfer of allogeneic (to the artery donor) human peripheral blood mononuclear cells. Interferon-gamma -dependent rejection ensues within 4 weeks, characterized by intimal thickening, T-cell infiltrates, and vascular cell activation, a response resembling clinical intimal arteritis. The PPAR gamma agonists 15-deoxy-prostaglandin-J(2), ciglitazone, and pioglitazone reduced intimal expansion, intimal infiltration of CD45RO(+) memory T cells, and plasma levels of inflammatory cytokines. The PPAR gamma antagonist GW9662 reversed the protective effects of PPAR gamma agonists, confirming the involvement of PPAR gamma -mediated pathways. In vitro, pioglitazone inhibited both alloantigen-induced proliferation and superantigen-induced transendothelial migration of memory T cells, indicating the potential mechanisms of PPAR gamma effects. Conclusion-Our results suggest that PPAR gamma agonists inhibit allogeneic human memory T cell responses and may be useful for the treatment of vascular graft rejection.
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