title: In vivo imaging of the molecular distribution of the VEGF receptor during angiogenesis in a mouse model of ischemia.
abstract: Vascular endothelial growth factor (VEGF) plays a critical role in angiogenesis and has been applied to medical therapy. However, because vascular imaging at the molecular level is impossible, the detailed in vivo dynamics of VEGF and its receptor (VEGFR) remain unknown. In this study, to understand the molecular distribution of VEGF and the VEGFR, we prepared ischemic mice with a new surgical method and induced angiogenesis in the gastrocnemius muscle. Then, we made a VEGF-conjugated fluorescence nanoparticle and performed staining of VEGFR-expressing cells with the fluorescent probe, demonstrating the high affinity of the probe for VEGFR. To observe the physiologic molecular distribution of VEGFR, we performed in vivo single-particle imaging of gastrocnemius in the ischemic leg with the fluorescent probe. The results suggested that only a 3-fold difference of VEGFR distribution is involved in the formation of branched vasculature in angiogenesis, although previous ex vivo data showed a 13-fold difference in its distribution, indicating that a method inducing a several-fold local increase of VEGFR concentration may be effective in generating site-specific angiogenesis in ischemic disease. This new in vivo imaging of ischemic mice could make useful contributions to understanding the mechanisms of angiogenesis and to developing a VEGFR-related drug.
authors.affiliation: Department of Nano-Medical Science, Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Hamada
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Gonda
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeda
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yambe
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D035002:Lower Extremity / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D040262:Receptors, Vascular Endothelial Growth Factor