Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup
Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup
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DOI：
10.1161/atvbaha.114.304857
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发表时间：
2015-06-01
影响因子：
8.7
通讯作者：
Kiessling, Fabian
中科院分区：
文献类型：
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作者：
Curaj, Adelina;Wu, Zhuojun;Kiessling, Fabian
心血管介入会导致血管壁损伤，因此在内皮完全恢复之前，抗血栓治疗是不可避免的。由于没有准确确定内皮状态的方法，许多患者接受长期抗凝治疗，从而无法进行任何侵入性医疗程序，例如外科手术和牙科干预。因此，我们的目的是引入分子超声成像的血管细胞粘附分子（VCAM）-1使用有针对性的聚正丁基氰基丙烯酸酯微泡（MBVCAM-1）作为一个容易访问的方法，以准确地监测reendothelialization的vessels. ApoE-/-小鼠喂食致动脉粥样硬化饮食1和12周，随后，内皮剥脱在颈动脉使用导丝进行。在剥脱后的不同时间点（1，3，7和14天）进行分子超声成像。MBVCAM-1结合在1天后增加，3天后达到峰值，7天后下降，饮食12周后，MBVCAM-1结合也在3天后达到峰值，但直到7天仍保持高水平，表明内皮恢复延迟。双荧光染色的双光子激光扫描显微镜成像证实了仅在愈合期动脉损伤后VCAM-1在浅表层上的暴露。完全再内皮化后，VCAM-1表达持续存在于内皮下层，但MBVCAM-1不再表达。结论-MBVCAM-1的分子超声成像有望评估血管损伤并监测动脉干预后的内皮恢复。因此，它可能成为一个重要的诊断工具，支持发展适当的治疗策略，个性化的抗凝和抗炎治疗后，心血管介入。
Objective-Cardiovascular interventions induce damage to the vessel wall making antithrombotic therapy inevitable until complete endothelial recovery. Without a method to accurately determine the endothelial status, many patients undergo prolonged anticoagulation therapy, denying them any invasive medical procedures, such as surgical operations and dental interventions. Therefore, we aim to introduce molecular ultrasound imaging of the vascular cell adhesion molecule (VCAM)-1 using targeted poly-n-butylcyanoacrylate microbubbles (MBVCAM-1) as an easy accessible method to monitor accurately the reendothelialization of vessels.Approach and Results-ApoE-/-mice were fed with an atherogenic diet for 1 and 12 weeks and subsequently, endothelial denudation was performed in the carotid arteries using a guidewire. Molecular ultrasound imaging was performed at different time points after denudation (1, 3, 7, and 14 days). An increased MBVCAM-1 binding after 1 day, a peak after 3 days, and a decrease after 7 days was found. After 12 weeks of diet, MBVCAM-1 binding also peaked after 3 days but remained high until 7 days, indicating a delay in endothelial recovery. Two-photon laser scanning microscopy imaging of double fluorescence staining confirmed the exposure of VCAM-1 on the superficial layer after arterial injury only during the healing phase. After complete reendothelialization, VCAM-1 expression persisted in the subendothelial layer but was not reachable for the MBVCAM-1 anymore.Conclusion-Molecular ultrasound imaging with MBVCAM-1 is promising to assess vascular damage and to monitor endothelial recovery after arterial interventions. Thus, it may become an important diagnostic tool supporting the development of adequate therapeutic strategies to personalize anticoagulant and anti-inflammatory therapy after cardiovascular intervention.