Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease.
Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease.
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DOI：
10.1161/atvbaha.109.196386
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Lindner JR
中科院分区：
文献类型：
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作者：
Kaufmann BA;Carr CL;Belcik JT;Xie A;Yue Q;Chadderdon S;Caplan ES;Khangura J;Bullens S;Bunting S;Lindner JR
我们假设内皮细胞粘附分子表达的分子成像可以无创地评估病变前促动脉粥样硬化表型。ldl受体和apobec1编辑肽缺失小鼠（DKO小鼠）作为年龄依赖性动脉粥样硬化模型进行了研究。在10、20和40周龄时，使用针对p -选择素和VCAM-1的造影剂对近段胸主动脉进行超声分子成像。通过超高频超声、组织学和免疫组织化学评估动脉粥样硬化病变的严重程度和含量。在所有年龄的野生型小鼠中，既没有主动脉增厚，也没有靶向示踪信号增强。在DKO小鼠中，病变在10周时从稀疏的轻度内膜增厚发展到40周时广泛的严重病变并伴有腔内侵犯。p -选择素和VCAM-1的分子成像在DKO小鼠的所有年龄均显示选择性信号增强（与非靶向药物相比p<0.01）。DKO小鼠的p -选择素和VCAM-1信号在10周时比野生型小鼠高3倍，在20周时高4 - 6倍，在40周时高9 - 10倍。面部显微镜显示靶向微泡优先附着于病变形成区域。内皮激活的无创超声分子成像可以在梗阻性动脉粥样硬化病变出现之前检测出病变易感的血管表型。
We hypothesized that molecular imaging of endothelial cell adhesion molecule expression could non-invasively evaluate pre-lesion pro-atherogenic phenotype. Mice deficient for the LDL-receptor and the Apobec-1 editing peptide (DKO mice) were studied as an age-dependent model of atherosclerosis. At 10, 20, and 40 weeks of age, ultrasound molecular imaging of the proximal thoracic aorta was performed with contrast agents targeted to P-selectin and VCAM-1. Atherosclerotic lesion severity and content were assessed by ultra-high frequency ultrasound, histology, and immunohistochemistry. In wild-type mice at all ages, there was neither aortic thickening nor targeted tracer signal enhancement. In DKO mice, lesions progressed from sparse mild intimal thickening at 10 weeks to widespread severe lesions with luminal encroachment at 40 weeks. Molecular imaging for P-selectin and VCAM-1 demonstrated selective signal enhancement (p<0.01 vs. non-targeted agent) at all ages for DKO mice. P-selectin and VCAM-1 signal in DKO mice were greater by 3-fold at 10 wks, 4–6-fold at 20 wks, and 9–10-fold at 40 weeks compared to wild-type mice. En face microscopy demonstrated preferential attachment of targeted microbubbles to regions of lesion formation. Non-invasive ultrasound molecular imaging of endothelial activation can detect lesion-prone vascular phenotype before the appearance of obstructive atherosclerotic lesions.