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Interferon-gamma-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients
Zhou, Jing1; Qin, Lingfeng1; Yi, Tai2,6; Ali, Rahmat1; Li, Qingle1,7; Jiao, Yang1,7; Li, Guangxin1; Tobiasova, Zuzana2; Huang, Yan3; Zhang, Jiasheng3; Yun, James J.1,4,5; Sadeghi, Mehran M.3,4,5; Giordano, Frank J.3,4,5; Pober, Jordan S.2,4; Tellides, George1,4,5
关键词atherosclerosis cardiovascular disease interferons lymphocytes transplantation
刊名CIRCULATION RESEARCH
2015-11-06
DOI10.1161/CIRCRESAHA.115.306932
117期:11页:943-955
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Hematology ; Peripheral Vascular Disease
资助者American Heart Association Scientist Development Grant ; National Institutes of Health ; Yale University Department of Surgery and Section of Cardiac Surgery ; American Heart Association Scientist Development Grant ; National Institutes of Health ; Yale University Department of Surgery and Section of Cardiac Surgery
研究领域[WOS]Cardiovascular System & Cardiology ; Hematology
关键词[WOS]E-DEFICIENT MICE ; CORONARY-ARTERY-DISEASE ; ISCHEMIC-HEART-DISEASE ; FRAMINGHAM RISK SCORE ; E KNOCKOUT MICE ; RENAL-TRANSPLANTATION ; APOLIPOPROTEIN-E ; KIDNEY-TRANSPLANT ; MOUSE HEARTS ; GRAFT LOSS
英文摘要

Rationale: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors.

Objective: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients.

Methods and Results: We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon- and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon- after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host.

Conclusions: Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.

语种英语
所属项目编号13SDG17170019 ; RO1-HL109455
资助者American Heart Association Scientist Development Grant ; National Institutes of Health ; Yale University Department of Surgery and Section of Cardiac Surgery ; American Heart Association Scientist Development Grant ; National Institutes of Health ; Yale University Department of Surgery and Section of Cardiac Surgery
WOS记录号WOS:000364317000008
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63121
专题北京大学第二临床医学院_血管外科
作者单位1.Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA
2.Nationwide Childrens Hosp, Res Inst, Columbus, MS USA
3.Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
4.Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA
5.Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA
6.Yale Univ, Sch Med, Interdepartmental Program Vasc Biol & Therapeut, New Haven, CT USA
7.Peking Univ, Peoples Hosp, Dept Vasc Surg, Beijing 100871, Peoples R China
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GB/T 7714
Zhou, Jing,Qin, Lingfeng,Yi, Tai,et al. Interferon-gamma-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients[J]. CIRCULATION RESEARCH,2015,117(11):943-955.
APA Zhou, Jing.,Qin, Lingfeng.,Yi, Tai.,Ali, Rahmat.,Li, Qingle.,...&Tellides, George.(2015).Interferon-gamma-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients.CIRCULATION RESEARCH,117(11),943-955.
MLA Zhou, Jing,et al."Interferon-gamma-Mediated Allograft Rejection Exacerbates Cardiovascular Disease of Hyperlipidemic Murine Transplant Recipients".CIRCULATION RESEARCH 117.11(2015):943-955.
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