Molecular Magnetic Resonance Imaging of Myocardial Angiogenesis After Acute Myocardial Infarction
Molecular Magnetic Resonance Imaging of Myocardial Angiogenesis After Acute Myocardial Infarction
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DOI：
10.1161/circulationaha.109.889451
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发表时间：
2010-02-16
期刊：
影响因子：
37.8
通讯作者：
Backes, Walter H.
中科院分区：
文献类型：
--
作者：
Oostendorp, Marlies;Douma, Kim;Backes, Walter H.
血管新生是急性心肌梗死（MI）后恢复缺血心肌灌注的自然机制。治疗性血管生成正在探索作为一种新的治疗心肌梗死患者，然而，敏感的，非侵入性的治疗效果的体内措施缺乏，需要开发。在这里，提出了一种分子磁共振成像方法，以非侵入性成像血管生成活性在体内的小鼠模型MI与环Asn-Gly-Arg（cNGR）标记的顺磁性量子点（pQD）。三肽cNGR家园特异性CD 13，一种氨基肽酶，是强烈上调心肌angiogenesization.Methods和Results-Acute MI诱导在雄性瑞士小鼠通过永久结扎左冠状动脉前降支。在手术后7天和静脉注射造影剂后2小时内进行分子磁共振成像。注射cNGR-pQD导致主要位于梗死心肌中的强阴性对比。在注射未标记的pQD的MI小鼠和注射cNGR-pQD的假手术小鼠中，这种阴性对比显著更少。离体双光子激光扫描显微镜验证显示cNGR-pQD与血管内皮细胞的强烈共定位，而未标记的pQD大多外渗并扩散通过组织。此外，2-光子激光扫描显微镜表现出显着的微血管重塑在梗死/边缘区相比，远程myocardial.Conclusions-cNGR-pQDs允许选择性的，非侵入性的检测血管生成活性在梗死的心脏与使用在体内的分子磁共振成像和离体2-光子激光扫描显微镜。（循环。2010; 121：775-783）。
Background-Angiogenesis is a natural mechanism to restore perfusion to the ischemic myocardium after acute myocardial infarction (MI). Therapeutic angiogenesis is being explored as a novel treatment for MI patients; however, sensitive, noninvasive in vivo measures of therapeutic efficacy are lacking and need to be developed. Here, a molecular magnetic resonance imaging method is presented to noninvasively image angiogenic activity in vivo in a murine model of MI with cyclic Asn-Gly-Arg (cNGR)-labeled paramagnetic quantum dots (pQDs). The tripeptide cNGR homes specifically to CD13, an aminopeptidase that is strongly upregulated during myocardial angiogenesis.Methods and Results-Acute MI was induced in male Swiss mice via permanent ligation of the left anterior descending coronary artery. Molecular magnetic resonance imaging was performed 7 days after surgery and up to 2 hours after intravenous contrast agent administration. Injection of cNGR-pQDs resulted in a strong negative contrast that was located mainly in the infarcted myocardium. This negative contrast was significantly less in MI mice injected with unlabeled pQDs and in sham-operated mice injected with cNGR-pQDs. Validation with ex vivo 2-photon laser scanning microscopy revealed a strong colocalization of cNGR-pQDs with vascular endothelial cells, whereas unlabeled pQDs were mostly extravasated and diffused through the tissue. Additionally, 2-photon laser scanning microscopy demonstrated significant microvascular remodeling in the infarct/border zones compared with remote myocardium.Conclusions-cNGR-pQDs allow selective, noninvasive detection of angiogenic activity in the infarcted heart with the use of in vivo molecular magnetic resonance imaging and ex vivo 2-photon laser scanning microscopy. (Circulation. 2010; 121: 775-783.)