Synergistically combined gene delivery for enhanced VEGF secretion and antiapoptosis.
Synergistically combined gene delivery for enhanced VEGF secretion and antiapoptosis.
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DOI：
10.1021/mp400178m
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发表时间：
2013-10-07
影响因子：
4.9
通讯作者：
Kim SW
中科院分区：
文献类型：
--
作者：
Won YW;Lee M;Kim HA;Nam K;Bull DA;Kim SW
以目前的药物治疗，防止左心室重塑和进展为心力衰竭是一项艰巨的任务。基因治疗被认为是缺血性心脏病长期并发症的直接治疗方法。尽管目前使用单分子靶点的基因疗法似乎是可能的，但它们在治疗缺血性疾病方面尚未取得成功。以高效聚合基因载体PAM-ABP为载体，设计协同联合基因递送策略，增强血管内皮生长因子（VEGF）分泌，延长抗凋亡作用。本研究将表达缺氧诱导血红素加氧酶-1 （HO-1）和含有酪氨酸磷酸酶-1 microRNA的Src同源结构域-2 （mishp1）的缺氧诱导质粒与缺氧反应性VEGF质粒结合在一起。HO-1与VEGF之间的正反馈回路以及SHP-1在血管生成中的负调控作用协同促进VEGF的分泌。在缺氧心肌细胞和缺氧心肌细胞凋亡中证实了基因结合和HO-1活性延长对VEGF分泌的协同作用，并且协同作用减弱。这些结果提示，VEGF、HO-1和mshp -1的协同联合可能在缺血性疾病的临床治疗中有前景。
With current pharmacological treatments, preventing the remodeling of the left ventricle and the progression to heart failure is a difficult task. Gene therapy is considered to provide a direct treatment to the long-term complications of ischemic heart diseases. Although current gene therapies that use single molecular targets seem potentially possible, they have not achieved a success in the treatment of ischemic diseases. With an efficient polymeric gene carrier, PAM-ABP, we designed a synergistically combined gene delivery strategy to enhance vascular endothelial growth factor (VEGF) secretion and prolong anti-apoptotic effects. A hypoxia-inducible plasmid expressing both hypoxia-inducible heme oxygenase-1 (HO-1) and the Src homology domain-2 containing tyrosine phosphatase-1 microRNA (miSHP 1) and a hypoxia-responsive VEGF plasmid were combined in this study. The positive feedback circuit between HO-1 and VEGF, and the negative regulatory role of SHP-1 in angiogenesis enhance VEGF secretion synergistically. The synergy in VEGF secretion as a consequence of the gene combination and the prolonged HO-1 activity was confirmed in hypoxic cardiomyocytes and cardiomyocyte apoptosis under hypoxia, and was decreased synergistically. These results suggest that the synergistic combination of VEGF, HO-1, and miSHP-1 may be promising for the clinical treatment of ischemic diseases.
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影响因子：
5
作者：
Lin, Heng-Huei;Chen, Yen-Hui;Chau, Lee-Young
通讯作者：
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影响因子：
64.5
作者：
KLINGMULLER, U;LORENZ, U;LODISH, HF
通讯作者：
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影响因子：
14
作者：
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通讯作者：
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20.3
作者：
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5.3
作者：
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