Alphavbeta3-targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study.
Alphavbeta3-targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study.
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Alphavbeta3 靶向检测移植人冠状动脉中的动脉病变：一项放射自显影研究。
DOI：
10.1096/fj.05-4130fje
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Sadeghi,
中科院分区：
文献类型：
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作者：
Zhang,Jiasheng;Krassilnikova,Svetlana;Gharaei,AmirA;Fassaei,HoomanRastegar;Esmailzadeh,Leila;Asadi,Abolfazl;Edwards,DScott;Harris,ThomasD;Azure,Michael;Tellides,George;Sinusas,AlbertJ;Zaret,BarryL;Bender,JeffreyR;Sadeghi,
以冠状动脉弥漫性向心性狭窄为特征的移植物动脉病(GA)是心脏移植术后远期移植物失败的主要原因。αvβ3整合素在增殖的血管细胞中表达上调，可能成为GA成像的合适靶点。我们使用了人/鼠嵌合GA模型，在该模型中，将人冠状动脉的片段移植到严重联合免疫缺陷小鼠，然后与同种异体人外周血单个核细胞(PBMC)重建。这导致了血管重塑，其特征是在4wk期间形成新的内膜。α-v-β-3在无外周血单核细胞移植的动物移植物中的表达最低，重建后2wk时显著增加，4wk时降至基线水平。2wk时细胞增殖最强，与α-v-β-3表达峰值相关。将111In标记的αvβ3(活性构象)靶向放射性示踪剂RP748分别于重建后0、2、4wk注入5组受者。移植物/自体主动脉的相对摄取，定义为放射自显影强度，密切跟踪了增殖过程。使用过量的非标记示踪剂证明摄取的特异性。总之，αvβ3整合素在GA中瞬时上调(并激活)，并可能成为RP748的靶点，用于检测GA早期的增殖过程。
Graft arteriopathy (GA), characterized by diffuse concentric narrowing of coronary arteries, is the major cause of late graft failure in cardiac transplantation. αvβ3 Integrin is up‐regulated in proliferating vascular cells and may constitute an appropriate target for imaging GA. We used a human/mouse chimeric model of GA, in which segments of human coronary artery were transplanted to severe combined immunodeficiency mice, followed by reconstitution with allogeneic human peripheral blood mononuclear cells (PBMC). This led to vascular remodeling characterized by neointima formation over a period of 4 wk. αvβ3 expression in the graft was minimal in animals without PBMC, considerably increased by 2 wk, and decreased toward baseline by 4 wk after PBMC reconstitution. Cell proliferation was maximal at 2 wk, correlating with peak αvβ3 expression. RP748, an111In‐labeled αvβ3 (active conformation)‐targeted radiotracer was injected into groups of 5 recipients at 0, 2, and 4 wk after PBMC reconstitution. Relative uptakes, defined as autoradiographic intensity in the graft/native aortas closely tracked the proliferative process. Specificity of uptake was demonstrated using excess nonlabeled tracer. In conclusion, αvβ3 integrin is transiently up‐regulated (and activated) in GA and may be targeted by RP748 for detection of the proliferative process in early GA.