Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm.
Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm.
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DOI：
10.7150/thno.55106
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发表时间：
2021
期刊：
影响因子：
12.4
通讯作者：
Sadeghi MM
中科院分区：
文献类型：
--
作者：
Toczek J;Boodagh P;Sanzida N;Ghim M;Salarian M;Gona K;Kukreja G;Rajendran S;Wei L;Han J;Zhang J;Jung JJ;Graham M;Liu X;Sadeghi MM
炎症在包括腹主动脉瘤（AAA）在内的几种血管病变的发病机制中起着重要作用。评估炎症在AAA病理生物学中的作用和体内潜在的结果需要非侵入性的高分辨率成像工具。我们研究了利用纳米颗粒造影剂对吞噬活性的x射线计算机断层扫描（CT）成像预测AAA预后的可行性。方法：在巨噬细胞细胞系中观察几种纳米颗粒CT造影剂的摄取情况。最有希望的药物Exitron nano 12000在体外进一步表征，并用于随后的体内试验。通过血管紧张素II （Ang II）输注Apoe-/-小鼠诱导AAA长达4周。通过CT成像评估注入angii的Apoe-/-小鼠在AAA中的生物分布和摄取。成像后，采集主动脉组织，进行形态测定、透射电镜和基因表达分析。一组注射了Ang II的Apoe-/-小鼠在注射Ang II的第一周内进行了纳米颗粒增强CT成像，并在4周时评估了它们的生存和主动脉外径，以探讨血管壁CT增强在预测AAA预后中的价值。结果：Exitron纳米12000在巨噬细胞中有特异性摄取。CT显示在单核吞噬细胞丰富的组织中可见纳米颗粒堆积。在纳米颗粒给药后的延迟CT图像上可以检测到主动脉壁增强，并与血管壁CD68表达相关。透射电镜证实了AAA外巨噬细胞中纳米颗粒的存在。在AAA诱导一周内获得的纳米颗粒诱导的CT增强图像可预测第4周的AAA预后。结论：通过建立基于ct的AAA吞噬活性分子成像的可行性，本研究将早期时间点图像上的炎症信号与AAA的进化联系起来。这项现成的技术克服了横截面、纵向和结果研究的一个重要障碍，不仅在AAA，而且在其他心血管疾病，促进了调节干预的评估，最终在临床转化，患者管理。
Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome in vivo requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome. Methods: Uptake of several nanoparticle CT contrast agents was evaluated in a macrophage cell line. The most promising agent, Exitron nano 12000, was further characterized in vitro and used for subsequent in vivo testing. AAA was induced in Apoe-/- mice through angiotensin II (Ang II) infusion for up to 4 weeks. Nanoparticle biodistribution and uptake in AAA were evaluated by CT imaging in Ang II-infused Apoe-/- mice. After imaging, the aortic tissue was harvested and used from morphometry, transmission electron microscopy and gene expression analysis. A group of Ang II-infused Apoe-/- mice underwent nanoparticle-enhanced CT imaging within the first week of Ang II infusion, and their survival and aortic external diameter were evaluated at 4 weeks to address the value of vessel wall CT enhancement in predicting AAA outcome. Results: Exitron nano 12000 showed specific uptake in macrophages in vitro. Nanoparticle accumulation was observed by CT imaging in tissues rich in mononuclear phagocytes. Aortic wall enhancement was detectable on delayed CT images following nanoparticle administration and correlated with vessel wall CD68 expression. Transmission electron microscopy ascertained the presence of nanoparticles in AAA adventitial macrophages. Nanoparticle-induced CT enhancement on images obtained within one week of AAA induction was predictive of AAA outcome at 4 weeks. Conclusions: By establishing the feasibility of CT-based molecular imaging of phagocytic activity in AAA, this study links the inflammatory signal on early time point images to AAA evolution. This readily available technology overcomes an important barrier to cross-sectional, longitudinal and outcome studies, not only in AAA, but also in other cardiovascular pathologies and facilitates the evaluation of modulatory interventions, and ultimately upon clinical translation, patient management.
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影响因子：
46.2
作者：
Behzadi S;Serpooshan V;Tao W;Hamaly MA;Alkawareek MY;Dreaden EC;Brown D;Alkilany AM;Farokhzad OC;Mahmoudi M
通讯作者：
Mahmoudi M
影响因子：
5.8
作者：
Kapellos, Theodore S.;Taylor, Lewis;Lee, Heyne;Cowley, Sally A.;James, William S.;Iqbal, Asif J.;Greaves, David R.
通讯作者：
Greaves, David R.
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H
影响因子：
7
作者：
Gautam, Anurag;van Veggel, Frank C. J. M.
通讯作者：
van Veggel, Frank C. J. M.
DOI：
10.1038/s41569-018-0064-2
发表时间：
2018-09
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
Ferrucci L;Fabbri E
通讯作者：
Fabbri E