INSERM U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, France.
Magn Reson Med. 2009 Nov;62(5):1195-201. doi: 10.1002/mrm.22103.
Vulnerable or high-risk atherosclerotic plaques often exhibit large lipid cores and thin fibrous caps that can lead to deadly vascular events when they rupture. In this study, polyethylene glycol (PEG)-micelles that incorporate a gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) amphiphile were used as an MR contrast agent. In an approach inspired by lipoproteins, the micelles were functionalized with tyrosine residues, an aromatic, lipophilic amino acid, to reach the lipid-rich areas of atherosclerotic plaque in a highly efficient manner. These micelles were applied to apolipoprotein E(-/-) (ApoE(-/-)) mice as a model of atherosclerosis. The abdominal aortas of the animals were imaged using T(1)-weighted (T(1)W) high-resolution MRI at 9.4T before and up to 48 h after the administration of the micelles. PEG-micelles modified with 15% tyrosine residues yielded a significant enhancement of the abdominal aortic wall at 6 and 24 h postinjection (pi) as compared to unmodified micelles. Fluorescence microscopy on histological sections of the abdominal aorta showed a correlation between lipid-rich areas and the distribution of the functionalized contrast agent in plaque. Using a simple approach, we demonstrated that lipid-rich areas in atherosclerotic plaque of ApoE(-/-) mice can be detected by MRI using Gd-DTPA micelles.
易损或高危动脉粥样硬化斑块通常表现为大的脂质核心和薄的纤维帽，当它们破裂时可能导致致命的血管事件。在这项研究中，聚乙二醇（PEG）胶束被用作磁共振对比剂，其中包含一种钆二乙三胺五乙酸（Gd-DTPA）两亲分子。受脂蛋白的启发，胶束被用酪氨酸残基官能化，酪氨酸是一种芳香、亲脂性氨基酸，以高效的方式到达动脉粥样硬化斑块的富含脂质区域。这些胶束被应用于载脂蛋白 E 基因敲除（ApoE(-/-)）小鼠作为动脉粥样硬化模型。在 9.4T 下使用 T(1)加权（T(1)W）高分辨率 MRI 对动物的腹主动脉进行成像，在给予胶束之前和之后最多 48 小时进行成像。与未修饰的胶束相比，修饰有 15%酪氨酸残基的 PEG 胶束在注射后 6 和 24 小时时使腹主动脉壁的增强显著。对腹主动脉组织学切片的荧光显微镜检查显示，富含脂质的区域与斑块中功能化对比剂的分布之间存在相关性。通过一种简单的方法，我们证明了使用 Gd-DTPA 胶束可以通过 MRI 检测 ApoE(-/-) 小鼠动脉粥样硬化斑块中的富含脂质区域。
