AIMS Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific MR contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed. METHODS AND RESULTS We utilised the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilation and performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement (LGE) MRI and T1 mapping at 3 Tesla, with subsequent ex vivo validation. In a cross-sectional study (n = 66; control=11, infused=55) we found that Gd-TESMA enhanced MRI was elevated and confined to dilated aortic segments (control: LGE=0.13±0.04mm2, control R1= 1.1±0.05s-1vs. dilated LGE =1.0±0.4mm2, dilated R1 =2.4±0.9s-1) and was greater in segments with medium (8.0±3.8mm3) and large (10.4±4.1mm3) compared to small (3.6±2.1mm3) vessel volume. Furthermore, a proof-of-principle longitudinal study (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expression in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment with pravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87±0.3mm2vs.1.0±0.44mm2) or aortic dilation (4.86±2.44mm3vs. 4.0±3.6mm3). Importantly, Gd-TESMA enhanced MRI identified accumulation of tropoelastin in excised human aneurysmal tissue (n = 4), which was confirmed histologically. CONCLUSION Tropoelastin MRI identifies dysfunctional matrix remodeling that is specifically expressed in regions of aortic aneurysm or dissection, and correlates with the development and rate of aortic expansion. Thus, it may provide an additive imaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with established aortopathy.

中文翻译：

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原弹性蛋白：腹主动脉扩张期间功能失调基质转换的体内成像标记。

AIMS 功能失调的基质转换存在于腹主动脉瘤 (AAA) 部位，并导致单体原弹性蛋白而非交联弹性蛋白的积累。我们使用基于钆的原弹性蛋白特异性 MR 造影剂 (Gd-TESMA) 来测试量化区域性原弹性蛋白周转率是否与小鼠模型中的主动脉扩张相关。还评估了 Gd-TESMA 与切除的人 AAA 的结合。方法和结果 我们利用血管紧张素 II (Ang II) 注入的载脂蛋白 E 基因敲除 (ApoE-/-) 小鼠主动脉扩张模型，并通过给予 Gd-TESMA 然后进行晚期钆增强 (LGE) MRI 进行原弹性蛋白的体内成像和 3 特斯拉的 T1 映射，随后进行体外验证。在一项横断面研究中（n = 66；对照 = 11，infused=55) 我们发现 Gd-TESMA 增强 MRI 升高并局限于扩张的主动脉段（对照：LGE=0.13±0.04mm2，对照 R1=1.1±0.05s-1vs.扩张的 LGE=1.0±0.4mm2，扩张的 R1 =2.4±0.9s-1)，与小 (3.6±2.1mm3) 容器体积相比，在中等 (8.0±3.8mm3) 和大 (10.4±4.1mm3) 段中更大。此外，一项使用 Gd-TESMA 增强 MRI 的原理验证纵向研究 (n = 19) 表明，与非扩张主动脉相比，扩张中的原弹性蛋白：弹性蛋白表达比例更高，这与主动脉扩张率相关。普伐他汀和阿司匹林 (n = 10) 治疗并未减少原弹性蛋白转换 (0.87±0.3mm2vs.1.0±0.44mm2) 或主动脉扩张 (4.86±2.44mm3vs. 4.0±3.6mm3)。重要的，Gd-TESMA 增强 MRI 确定了原弹性蛋白在切除的人动脉瘤组织中的积累 (n = 4)，这在组织学上得到了证实。结论 原弹性蛋白 MRI 可识别在主动脉瘤或夹层区域特异性表达的功能失调性基质重塑，并与主动脉扩张的发展和速度相关。因此，它可以为管腔直径的系列评估提供一个附加的成像标记，用于监测有主动脉病风险或已确定主动脉病的患者。