Detection of Injury-Induced Vascular Remodeling by Targeting Activated α v β 3 Integrin In Vivo Article (Web of Science)

abstract

  • Background— The α v β 3 integrin plays a critical role in cell proliferation and migration. We hypothesized that vascular cell proliferation, a hallmark of injury-induced remodeling, can be tracked by targeting α v β 3 integrin expression in vivo. Methods and Results— RP748, a novel 111 In-labeled α v β 3 -specific radiotracer, was evaluated for its cell-binding characteristics and ability to track injury-induced vascular proliferation in vivo. Three groups of experiments were performed. In cultured endothelial cells (ECs), TA145, a cy3-labeled homologue of RP748, localized to α v β 3 at focal contacts. Activation of α v β 3 by Mn 2+ led to increased EC binding of TA145. Left common carotid artery wire injury in apolipoprotein E −/− mice led to vascular wall expansion over a period of 4 weeks. RP748 (7.4 MBq) was injected into groups of 9 mice at 1, 3, or 4 weeks after left carotid injury, and carotids were harvested for autoradiography. Relative autographic intensity, defined as counts/pixel of the injured left carotid area divided by counts/pixel of the uninjured right carotid area, was higher at 1 and 3 weeks (1.8±0.1 and 1.9±0.2, respectively) and decreased significantly by 4 weeks after injury (1.4±0.1, P <0.05). Carotid α v and β 3 integrin expression was maximal at 1 week and decreased by 4 weeks after injury. The proliferation index, as determined by Ki67 staining, followed a temporal pattern similar to that of RP748 uptake. Dynamic gamma imaging demonstrated rapid renal clearance of RP748. Conclusions— RP748 has preferential binding to activated α v β 3 integrin and can track the injury-induced vascular proliferative process in vivo.

authors

  • Sadeghi, Mehran M.
  • Zhang, Jiasheng
  • Gharaei, Amir A.
  • Fassaei, Hooman Rastegar
  • Esmailzadeh, Leila
  • Kooshkabadi, Ali
  • Edwards, Scott
  • Yalamanchili, Padmaja
  • Harris, Thomas D.
  • Sinusas, Albert J.
  • Zaret, Barry L.
  • Bender, Jeffrey R.

publication date

  • 2004

webpage

published in

number of pages

  • 6

start page

  • 84

end page

  • 90

volume

  • 110

issue

  • 1