Over-expression of HO-1 on mesenchymal stem cells promotes angiogenesis and improves myocardial function in infarcted myocardium.
Over-expression of HO-1 on mesenchymal stem cells promotes angiogenesis and improves myocardial function in infarcted myocardium.
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间充质干细胞上HO-1的过表达促进梗死心肌血管生成并改善心肌功能
DOI：
10.1186/1423-0127-17-80
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发表时间：
2010-10-07
影响因子：
11
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
Zeng B;Lin G;Ren X;Zhang Y;Chen H
血红素加氧酶 - 1（HO - 1）是一种应激诱导酶，具有多种细胞保护作用，并且最近据报道在血管生成中具有重要作用。在此我们研究了间充质干细胞（MSCs）转导的HO - 1是否能在梗死心肌中诱导血管生成作用。使用腺病毒载体将HO - 1转染到培养的MSCs中。在心肌梗死1小时后，分别将1×10⁶个腺病毒 - HO - 1转染的MSCs（HO - 1 - MSCs）、腺病毒 - 空载体转染的MSCs（Null - MSCs）或磷酸盐缓冲液（PBS）心肌内注射到大鼠心脏中。结果显示，HO - 1 - MSCs能够在体外和体内诱导HO - 1的稳定表达。与Null - MSCs处理组和PBS处理组的心脏相比，HO - 1 - MSCs处理组心脏中的毛细血管密度以及血管生成生长因子血管内皮生长因子（VEGF）和成纤维细胞生长因子2（FGF2）的表达显著增强。然而，通过用HO抑制剂锌原卟啉处理动物，HO - 1的血管生成作用被消除。在HO - 1 - MSCs处理组的心脏中，心肌凋亡显著减少，纤维化面积显著减小；此外，HO - 1 - MSCs处理组心脏的心功能和重塑也得到显著改善。我们目前的研究结果支持这样一个前提，即MSCs转导的HO - 1能够在急性心肌梗死后诱导血管生成作用并改善心脏功能。
Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with diverse cytoprotective effects, and reported to have an important role in angiogenesis recently. Here we investigated whether HO-1 transduced by mesenchymal stem cells (MSCs) can induce angiogenic effects in infarcted myocardium. HO-1 was transfected into cultured MSCs using an adenoviral vector. 1 × 106 Ad-HO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was respectively injected into rat hearts intramyocardially at 1 h post-myocardial infarction. The results showed that HO-1-MSCs were able to induce stable expression of HO-1 in vitro and in vivo. The capillary density and expression of angiogenic growth factors, VEGF and FGF2 were significantly enhanced in HO-1-MSCs-treated hearts compared with Null-MSCs-treated and PBS-treated hearts. However, the angiogenic effects of HO-1 were abolished by treating the animals with HO inhibitor, zinc protoporphyrin. The myocardial apoptosis was marked reduced with significantly reduced fibrotic area in HO-1-MSCs-treated hearts; Furthermore, the cardiac function and remodeling were also significantly improved in HO-1-MSCs-treated hearts. Our current findings support the premise that HO-1 transduced by MSCs can induce angiogenic effects and improve heart function after acute myocardial infarction.
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影响因子：
5
作者：
Lin, Heng-Huei;Chen, Yen-Hui;Chau, Lee-Young
通讯作者：
Chau, Lee-Young
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Cooke, JP
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通讯作者：
Phillips, I