Molecular imaging of vasa vasorum neovascularization via DEspR-targeted contrast-enhanced ultrasound micro-imaging in transgenic atherosclerosis rat model.
Molecular imaging of vasa vasorum neovascularization via DEspR-targeted contrast-enhanced ultrasound micro-imaging in transgenic atherosclerosis rat model.
复制标题
DOI：
10.1007/s11307-010-0444-4
复制
发表时间：
2011-12
影响因子：
3.1
通讯作者：
Herrera, Victoria L. M.
中科院分区：
文献类型：
--
作者：
Decano, Julius L.;Moran, Anne Marie;Ruiz-Opazo, Nelson;Herrera, Victoria L. M.
关键词：
鉴于颈动脉滋养管新生血管与中风和心脏事件的风险增加相关，本体内研究旨在通过目标特异性对比增强超声（CEU）显微成像研究颈动脉滋养管新生血管的分子成像。使用双内皮素 1/VEGFsp 受体 (DEspR) 靶向微泡 (MBD) 以及 Vevo770 显微成像系统和 CEU 成像软件，对患有颈动脉疾病的雄性转基因大鼠和非转基因对照进行分子成像。在 13 只转基因大鼠中，有 7 只 DEspR 靶向 CEU 阳性成像表现出显着较高的对比强度信号 (CIS) 水平和破坏前/破坏后 CIS 差异，而对照同种型靶向微泡 (MBC)-CEU 成像 (n = 8) 和 5 只非转基因对照大鼠的 MBD CEU 成像中的 CIS 水平和差异显着降低 (P<0.0001)。离体免疫荧光分析证明 MBD 与 DEspR 阳性内皮细胞结合；以及 DEspR 靶向增强对比强度信号与血管滋养管新生血管和内膜病变中 DEspR 表达的关联。体外分析表明，MBD 与 DEspR 阳性人内皮细胞的结合呈剂量依赖性，与 MBC 或未标记的微泡相比，结合的细胞百分比和每个细胞的 MBD 数量不断增加 (P<0.0001)。体内 DEspR 靶向分子成像检测到患有颈动脉疾病的转基因大鼠的颈动脉病变和扩张的滋养血管新生血管中 DEspR 表达增加。未来的研究需要确定这种转基因动脉粥样硬化大鼠模型对中风或心脏病的预测价值以及转化应用。
Given that carotid vasa vasorum neovascularization is associated with increased risk for stroke and cardiac events, the present in vivo study was designed to investigate molecular imaging of carotid artery vasa vasorum neovascularization via target-specific contrast-enhanced ultrasound (CEU) micro-imaging. Molecular imaging was performed in male transgenic rats with carotid artery disease and non-transgenic controls using dual endothelin1/VEGFsp receptor (DEspR)-targeted microbubbles (MBD) and the Vevo770 micro-imaging system and CEU imaging software. DEspR-targeted CEU-positive imaging exhibited significantly higher contrast intensity signal (CIS)-levels and pre-/post-destruction CIS-differences in seven of 13 transgenic rats, in contrast to significantly lower CIS-levels and differences in control isotype-targeted microbubble (MBC)-CEU imaging (n =8) and in MBD CEU-imaging of five non-transgenic control rats (P<0.0001). Ex vivo immunofluorescence analysis demonstrated binding of MBD to DEspR-positive endothelial cells; and association of DEspR-targeted increased contrast intensity signals with DEspR expression in vasa vasorum neovessel and intimal lesions. In vitro analysis demonstrated dose-dependent binding of MBD to DEspR-positive human endothelial cells with increasing %cells bound and number of MBD per cell, in contrast to MBC or non-labeled microbubbles (P<0.0001). In vivo DEspR-targeted molecular imaging detected increased DEspR-expression in carotid artery lesions and in expanded vasa vasorum neovessels in transgenic rats with carotid artery disease. Future studies are needed to determine predictive value for stroke or heart disease in this transgenic atherosclerosis rat model and translational applications.
登录
查看更多内容
DOI：
10.1038/ncpcardio1246
发表时间：
2008-08
期刊：
NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE
影响因子：
--
作者：
Villanueva, Flordeliza S.;Wagner, William R.
通讯作者：
Wagner, William R.
一种使用对比增强的超声检查来评估鼠肿瘤模型中微脉管系统的方法。
DOI：
10.7863/jum.2008.27.12.1699
发表时间：
2008-12
期刊：
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
影响因子：
--
作者：
Loveless ME;Li X;Huamani J;Lyshchik A;Dawant B;Hallahan D;Gore JC;Yankeelov TE
通讯作者：
Yankeelov TE
影响因子：
2.9
作者：
Piedra, Mark;Allroggen, Achim;Lindner, Jonathan R.
通讯作者：
Lindner, Jonathan R.
影响因子：
19.7
作者：
Hauff, P;Reinhardt, M;Schirner, M
通讯作者：
Schirner, M
影响因子：
37.8
作者：
Ellegala, DB;Poi, HL;Lindner, JR
通讯作者：
Lindner, JR