title: Suppression of cardiac allograft vasculopathy in mice by inhibition of CC-motif chemokine receptor 5.
abstract: Cardiac allograft vasculopathy (CAV) is the leading cause of late morbidity and mortality in heart-transplant patients. Increasing evidences support the important role of chemokines and their receptors in transplant immunology. Chemokine-chemokine receptor interaction and subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts. In this study, we first inhibited CC-motif chemokine receptor 5 (CCR5) expression by using lentiviral-mediated gene transfer of an anti-CCR5 siRNA, which introduced through CD34(+) hematopoietic stem/progenitor cell transplantation. Stably marked lymphocytes expressing siRNA and consistent downregulation of CCR5 expression were detected. Our results showed that survival was significantly prolonged in CCR5 knock-down mice and donor hearts from siRNA-treated mice developed markedly less CAV. Infiltration of CD4(+) and CD8(+) T-lymphocytes into transplanted hearts was also markedly decreased. These findings suggest that CCR5 plays an important role in CAV development and inhibition of this chemokine could improve long-term survival after cardiac transplantation.
authors.affiliation: Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Bao
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiaquan
authors.initials: J
authors.lastname: Zhu
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
authors.forename: Yunjiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020868:Gene Silencing; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D006331:Heart Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016027:Heart Transplantation / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016086:Lentivirus; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic; D014184:Transplantation, Homologous
chemical_list: D034741:RNA, Small Interfering; D019713:Receptors, CCR5