Ultrasound Detection of Myocardial Ischemic Memory Using an E-Selectin Targeting Peptide Amenable to Human Application
Ultrasound Detection of Myocardial Ischemic Memory Using an E-Selectin Targeting Peptide Amenable to Human Application
复制标题
使用适合人类应用的 E-选择素靶向肽对心肌缺血记忆进行超声检测
DOI：
10.2310/7290.2014.00006
复制
发表时间：
2014-06-01
影响因子：
2.8
通讯作者：
Villanueva, Flordeliza S.
中科院分区：
文献类型：
--
作者：
Leng, Xiaoping;Wang, Jianjun;Villanueva, Flordeliza S.
血管内皮细胞白细胞黏附分子，如E-选择素，在心肌缺血/再灌流过程中显著上调，因此是近期心肌缺血的“缺血记忆”生物标志物。我们试图开发一种以E-选择素为靶点的微泡(MBS)组成的超声分子显像剂，以使原因不明的胸痛患者能够鉴别诊断心肌缺血。制备了具有人E-选择素亲和力的多肽(MBESEL)的可生物降解聚合物MBS。对照MBS为杂乱肽(MBCTL)或非特异性免疫球蛋白G(MBIgG)。MBESEL与激活的大鼠内皮细胞(ECs)的粘附力在体外流动系统中和体内用大鼠提睾体微循环的活体显微镜证实。在短暂(15分钟)冠状动脉闭塞后4小时对大鼠近期心肌缺血进行超声分子成像。MBESEL对炎症内皮细胞的粘附率高于正常内皮细胞，而MBCTL和MBIg G对炎症内皮细胞的粘附率与正常内皮细胞无差异。在任何条件下，MBESEL对炎症微循环的粘附率均高于非炎症微循环，而对MBCTL或MBIg的粘附率最低。注射MBSEL后的超声成像显示先前缺血区持续的对比增强。MBESEL组缺血后心肌的视频强度高于非缺血组(11.6+/-2.7dBvs 3.6+/-0.8dBp<；02)，也高于MBCTL组(4.0+/-1.0db，p<；0.03)和MBIg G组(1.7+/-0.1db，p<；03)。通过具有人E-选择素结合亲和力的短合成多肽靶向E-选择素的MBS使超声心动图能够检测最近的缺血，为临床心肌缺血记忆成像识别急性冠脉综合征奠定了基础。
Vascular endothelial leukocyte adhesion molecules, such as E-selectin, are acutely upregulated in myocardial ischemia/reperfusion and are thus "ischemic memory" biomarkers for recent cardiac ischemia. We sought to develop an ultrasound molecular imaging agent composed of microbubbles (MBs) targeted to E-selectin to enable the differential diagnosis of myocardial ischemia in patients presenting with chest pain of unclear etiology. Biodegradable polymer MBs were prepared bearing a peptide with specific human E-selectin affinity (MBESEL). Control MBs had scrambled peptide (MBCTL) or nonspecific IgG (MBIgG). MBESEL adhesion to activated rat endothelial cells (ECs) was confirmed in vitro in a flow system and in vivo with intravital microscopy of rat cremaster microcirculation. Ultrasound molecular imaging of recent myocardial ischemia was performed in rats 4 hours after transient (15 minutes) coronary occlusion. MBESEL adhesion was higher to inflamed versus normal ECs in vitro; there was no difference in MBCTL or MBIgG adhesion to inflamed versus normal ECs. There was greater adhesion of MBESEL to inflamed versus noninflamed microcirculation and minimal adhesion of MBCTL or MBIgG under any condition. Ultrasound imaging after injection of MBSEL demonstrated persistent contrast enhancement of the previously ischemic region. Videointensity in postischemic myocardium after MBESEL was higher than that in the nonischemic bed (11.6 +/- 2.7 dB vs 3.6 +/- 0.8 dB, p < .02) and higher than that after MBCTL (4.0 +/- 1.0 dB, p < .03) or MBIgG (1.7 +/- 0.1 dB, p < 03). MBs targeted to E-selectin via a short synthetic peptide with human E-selectin binding affinity enables echocardiographic detection of recent ischemia, setting the stage for clinical myocardial ischemic memory imaging to identify acute coronary syndromes.