0 36

Cited 8 times in

Molecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis

Authors
 Chi Young Shim ; Ya Ni Liu ; Jonathan R. Lindner ; Zaverio Ruggeri ; Adam Munday ; José A. López ; Yue Qi ; Mackenzie Treible ; Brian P. Davidson ; Ted Foster ; Aris Xie ; Tamara Atkinson 
Citation
 Circulation-Cardiovascular Imaging, Vol.8(7) : e002765, 2015 
Journal Title
 Circulation-Cardiovascular Imaging 
ISSN
 1941-9651 
Issue Date
2015
Abstract
BACKGROUND: Nonthrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet preactivation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways. METHODS AND RESULTS: Mice deficient for the low-density lipoprotein receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 weeks of age, which provided progressive increase in stage from early fatty streak (10 weeks) to large complex plaques without rupture (40 weeks). Platelet-targeted contrast ultrasound molecular imaging of the thoracic aorta performed with microbubbles targeted to GPIbα demonstrated selective signal enhancement as early as 10 weeks of age. This signal increased progressively with age (almost 8-fold increase from 10 to 40 weeks, analysis of variance P<0.001). Specificity for platelet targeting was confirmed by the reduction in platelet-targeted signal commensurate with the decrease in platelet count after immunodepletion with anti-GPIb or anti-CD41 antibody. Inhibition of P-selectin in 20 and 40 weeks atherosclerotic mice resulted in a small (15% to 30%) reduction in platelet signal. Molecular imaging with microbubbles targeted to the A1 domain of von Willebrand factor demonstrated selective signal enhancement at all time points, which did not significantly increase with age. Treatment of 20 and 40 week mice with recombinant ADAMTS13 eliminated platelet and von Willebrand factor molecular imaging signal. CONCLUSIONS: Platelet-endothelial interactions occur in early atherosclerosis. These interactions are in part caused by endothelial von Willebrand factor large multimers, which can be reversed with exogenous ADAMTS13.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140861
DOI
10.1161/CIRCIMAGING.114.002765
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
사서에게 알리기
  feedback
Link
 http://circimaging.ahajournals.org/content/8/7/e002765.long
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse