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αvβ3‐Targeted detection of arteriopathy in transplanted human coronary arteries: an autoradiographic study
Author(s) -
Zhang Jiasheng,
Krassilnikova Svetlana,
Gharaei Amir A.,
Fassaei Hooman Rastegar,
Esmailzadeh Leila,
Asadi Abolfazl,
Scott Edwards D.,
Harris Thomas D.,
Azure Michael,
Tellides George,
Sinusas Albert J.,
Zaret Barry L.,
Bender Jeffrey R.,
Sadeghi Mehran M.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4130fje
Subject(s) - neointima , peripheral blood mononuclear cell , artery , coronary arteries , integrin , transplantation , medicine , pathology , blood vessel , chemistry , receptor , restenosis , in vitro , biochemistry , stent
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, an 111 In‐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.