Detection of antecedent myocardial ischemia with multiselectin molecular imaging.
Detection of antecedent myocardial ischemia with multiselectin molecular imaging.
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DOI：
10.1016/j.jacc.2012.07.027
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发表时间：
2012-10-23
影响因子：
24
通讯作者：
Lindner, Jonathan R.
中科院分区：
文献类型：
--
作者：
Davidson, Brian P.;Kaufmann, Beat A.;Belcik, J. Todd;Xie, Aris;Qi, Yue;Lindner, Jonathan R.
我们的目的是开发一种超声心动图分子成像方法检测近期心肌缺血，使用重组P-选择素糖蛋白配体（PSGL）-1作为靶向配体，这是一种可行的方法，为人类使用。使用人PSGL-1作为靶向部分的缺血记忆成像可以通过靶向早期（P-选择素）和晚期（E-选择素）内皮缺血反应来延长缺血后检测的时间窗。制备携带重组人PSGL-1（MBYSPSL）或P-选择素抗体（MBAb）的脂质微泡。通过使用流动室和活体显微镜评价靶向附着。在短暂缺血再灌注损伤后45至360分钟，首先在野生型和P-选择素缺陷（P-/-）小鼠的后肢进行体内超声分子成像。心肌声学造影分子显像分别在短暂的左前降支冠状动脉缺血再灌注后1.5、3、6和18 h进行。MBAb和MBYSPSL在流动室实验（剪切应力0.5至8.0达因/厘米2）中与P-选择素-免疫球蛋白G融合蛋白的微泡附着和在活体显微镜下与活化的微静脉内皮的微泡附着相似。在缺血后的肌肉中，MBAb和MBYSPSL观察到强烈的增强，并且随着时间的推移，MBYSPSL更加稳定。在心肌声学造影上，MBYSPSL和MBAb在缺血后90 min和3 h均产生类似的信号增强，这与缺血后危险区在空间上相关。信号显著降低，但在6至18 h时仍存在。使用携带重组人PSGL-1的人多选择素靶向造影剂的超声心动图分子成像可以在消退后数小时检测心肌缺血。这种方法可能被用于快速床旁评估近期胸痛患者。
Our aim was to develop an echocardiographic molecular imaging approach for detecting recent myocardial ischemia by using recombinant P-selectin glycoprotein ligand (PSGL)-1 as a targeting ligand, which is a feasible approach for human use. Ischemic memory imaging using human PSGL-1 as a targeting moiety may extend the time window for postischemic detection by targeting the early (P-selectin) and late (E-selectin) endothelial ischemic response. Lipid microbubbles bearing recombinant human PSGL-1 (MBYSPSL) or P-selectin antibody (MBAb) were prepared. Targeted attachment was evaluated by using flow chamber and intravital microscopy. In vivo ultrasound molecular imaging was first performed in the hindlimb in wild-type and P-selectin–deficient (P−/−) mice 45 to 360 min after brief ischemia-reperfusion injury. Myocardial contrast echocardiography molecular imaging was performed 1.5, 3, 6, and 18 h after brief left anterior descending coronary artery ischemia-reperfusion. Microbubble attachment to P-selectin–immunoglobulin G fusion protein in flow chamber experiments (shear stress 0.5 to 8.0 dyne/cm2) and to activated venular endothelium on intravital microscopy were similar for MBAb and MBYSPSL. Intense enhancement was seen for MBAb and MBYSPSL in postischemic muscle and was more stable over time for MBYSPSL. On myocardial contrast echocardiography, both MBYSPSL and MBAb produced similar signal enhancement at 90 min and 3 h after ischemia, which spatially correlated with the postischemic risk area. Signal significantly decreased but was still present at 6 to 18 h. Echocardiographic molecular imaging with a human multi-selectin–targeted contrast agent bearing recombinant human PSGL-1 can detect myocardial ischemia hours after resolution. This approach may potentially be used for rapid bedside evaluation of patients with recent chest pain.
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影响因子：
15.3
作者：
Ley, Klaus;Bullard, Dan C.;Arbones, Maria L.;Bosse, Roland;Vestweber, Dietmar;Tedder, Thomas F.;Beaudet, Arthur L.
通讯作者：
Beaudet, Arthur L.
DOI：
10.1016/j.echo.2010.03.013
发表时间：
2010-06
影响因子：
6.5
作者：
Wei, Kevin;Peters, Dawn;Belcik, Todd;Kalvaitis, Saul;Womak, Lisa;Rinkevich, Diana;Tong, Khim-Leng;Horton, Kenneth;Kaul, Sanjiv
通讯作者：
Kaul, Sanjiv
影响因子：
168.9
作者：
Eagle, KA;Goodman, SG;López-Sendón, J
通讯作者：
López-Sendón, J
影响因子：
37.8
作者：
Lindner, JR;Song, J;Ley, K
通讯作者：
Ley, K
DOI：
10.1152/ajpgi.2000.278.6.g878
发表时间：
2000-06-01
影响因子：
4.5
作者：
Russell, J;Epstein, CJ;Granger, DN
通讯作者：
Granger, DN