A molecular MRI probe to detect treatment of cardiac apoptosis in vivo.
A molecular MRI probe to detect treatment of cardiac apoptosis in vivo.
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DOI：
10.1002/mrm.22876
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发表时间：
2011-10
影响因子：
3.3
通讯作者：
Simpson, Paul C.
中科院分区：
文献类型：
--
作者：
Dash, Rajesh;Chung, Jaehoon;Chan, Trevor;Yamada, Mayumi;Barral, Joelle;Nishimura, Dwight;Yang, Phillip C.;Simpson, Paul C.
细胞凋亡引起的细胞死亡在心肌疾病中至关重要，早期可逆细胞凋亡的无创检测可能在临床上有用。外源性膜联蛋白-V (ANX) 蛋白与膜磷脂酰丝氨酸结合，在早期细胞凋亡中外化。用与重组人 ANX (ANX-SPIO) 缀合的超顺磁性氧化铁 (SPIO) 构建了分子 MRI 探针。在新生大鼠心室肌细胞、心脏成纤维细胞和间充质干细胞培养物以及小鼠心脏体内，用阿霉素（一种心脏毒性癌症药物）诱导细胞凋亡。 ANX-SPIO 使用 T2* 加权 3T MRI 进行验证。 ANX-SPIO 产生 T2* 信号丢失，反映铁含量，与独立的细胞凋亡标记物高度相关；通过竞争测定与凋亡肌细胞高亲和力结合（Ki 69nM）；比 TUNEL 染色更早地检测到培养物中的细胞凋亡；并揭示了成纤维细胞对细胞凋亡的抵抗力。随着体内细胞凋亡，ANX-SPIO 产生弥漫性心肌 T2* 信号丢失，这与铁染色和 caspase 活性增加相关。体内α-1-肾上腺素能激动剂治疗可逆转细胞凋亡并消除 ANX-SPIO MRI 信号。结论是，ANX-SPIO 的心脏 MRI 可以检测培养物和体内的早期非缺血性心脏细胞凋亡，并且可以在仍然可以治疗时识别患病心脏中可逆性损伤的心肌细胞。
Cell death by apoptosis is critical in myocardial diseases, and non-invasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, non-ischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible.
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影响因子：
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作者：
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