Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, Germany.
Circ Cardiovasc Imaging. 2011 Mar;4(2):147-55. doi: 10.1161/CIRCIMAGING.109.895607. Epub 2011 Mar 4.
The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951).
Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4; P<0.001). The area of enhancement correlated well with the area of remodeling obtained from histological data (R(2)=0.86, P<0.05).
We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.
细胞外基质（ECM）在动脉粥样硬化和支架内再狭窄的发病机制中起着重要作用。弹性蛋白是 ECM 的重要组成部分。ECM 降解可导致斑块不稳定，而增强的合成通常导致血管壁重构，导致支架植入后动脉狭窄或支架内再狭窄。本研究的目的是证明使用新型弹性蛋白结合对比剂（BMS-753951）进行血管重构 MRI 的可行性。
通过内皮剥脱和支架置入在 6 头猪中诱导冠状动脉损伤。在第 28 天，在注射钆二乙三胺五乙酸（Gd-DTPA）前后进行延迟增强 MRI 冠状动脉血管壁成像。两天后，在给予 BMS-753951 后重复 DE-MRI。确定对比噪声比和增强面积。BMS-753951 的延迟增强 MRI 导致主动脉、肺动脉和损伤的冠状动脉壁强烈增强，而 Gd-DTPA 则没有。与球囊损伤和对照冠状动脉相比，BMS-753951 对支架置入的冠状动脉进行延迟增强 MRI 时，对比噪声比提高了 3 倍（21±6 与 7±3 与 6±4；P<0.001）。增强面积与从组织学数据获得的重塑面积相关性良好（R²=0.86，P<0.05）。
我们在冠状动脉血管壁损伤的动物模型中证明了使用弹性蛋白特异性磁共振对比剂进行血管重塑的非侵入性检测和定量。这种新方法可能对疑似冠心病患者的冠状动脉血管壁重塑评估有用。现在需要在动脉粥样硬化动物模型和退行性 ECM 疾病中进行进一步研究。
