Thioredoxin 1 enhances neovascularization and reduces ventricular remodeling during chronic myocardial infarction: a study using thioredoxin 1 transgenic mice.
Thioredoxin 1 enhances neovascularization and reduces ventricular remodeling during chronic myocardial infarction: a study using thioredoxin 1 transgenic mice.
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DOI：
10.1016/j.yjmcc.2010.11.002
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发表时间：
2011-01
影响因子：
5
通讯作者：
Maulik N
中科院分区：
文献类型：
--
作者：
Adluri RS;Thirunavukkarasu M;Zhan L;Akita Y;Samuel SM;Otani H;Ho YS;Maulik G;Maulik N
氧化应激通过改变硫氧还蛋白-1（Trx 1）表达及其与心肌梗死（MI）后其他蛋白的相互作用在破坏新生血管形成中起着至关重要的作用。我们以前表明，Trx 1具有血管生成的特性，但在慢性心肌梗死过度表达Trx 1的可能的治疗意义尚未阐明。因此，我们探讨了血管生成和心肌保护的潜力，Trx 1在体内MI模型中使用过表达Trx 1的转基因小鼠。将野生型（W）和Trx 1转基因（Trx 1 Tg/+）小鼠随机分为W假手术（WS）、Trx 1 Tg/+假手术（TS）、TMI和TMI。永久性闭塞LAD冠状动脉诱发MI。过表达Trx 1的小鼠心脏显示纤维化和氧化应激减少，心肌细胞凋亡沿着减少，血管形成增加。我们发现，与WMI相比，TMI中Trx 1调节蛋白TXNIP和AKAP 12的表达受到显着抑制，并且p-Akt、p-eNOS和p-GSK-3β、HIF-1α、β-连环蛋白、VEGF、Bcl-2和生存素的表达增加。心肌梗死后30天进行的超声心动图显示，与TMI相比，TMI患者的心肌功能显著改善。我们的研究确定了Trx 1过表达及其与其调节蛋白TXNIP、AKAP 12以及随后Akt/GSK-3β/β-catenin/HIF-1α介导的VEGF和eNOS表达的激活在诱导血管生成和减少心室重构中的潜在作用。因此，Trx 1和我们研究中鉴定的其他蛋白可能被证明是治疗缺血性心脏病的潜在治疗靶点。
Oxidative stress plays a crucial role in disruption of neovascularization by alterations in thioredoxin-1 (Trx1) expression and its interaction with other proteins after myocardial infarction (MI). We previously showed that Trx1 has angiogenic properties, but the possible therapeutic significance of overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model using transgenic mice overexpressing Trx1. Wild type (W) and Trx1 transgenic (Trx1Tg/+) mice were randomized into W Sham (WS), Trx1Tg/+ Sham (TS), WMI and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress, and attenuated cardiomyocyte apoptosis along with increased vessel formation compared to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and AKAP 12, and increased p-Akt, p-eNOS and p-GSK-3β, HIF-1α, β-catenin, VEGF, Bcl-2 and survivin expression in TMI compared to WMI. Echocardiography performed 30 days after MI revealed significant improvement in myocardial functions in TMI compared to WMI. Our study identifies a potential role for Trx1 overexpression and its association with its regulatory proteins TXNIP, AKAP12 and subsequent activation of Akt/GSK-3β/β-catenin/HIF-1α-mediated VEGF and eNOS expression in inducing angiogenesis and reduced ventricular remodeling. Hence, Trx1 and other proteins identified in our study may prove to be potential therapeutic targets in the treatment of ischemic heart disease.
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影响因子：
7.7
作者：
Samuel SM;Akita Y;Paul D;Thirunavukkarasu M;Zhan L;Sudhakaran PR;Li C;Maulik N
通讯作者：
Maulik N
影响因子：
5
作者：
Katare R;Caporali A;Emanueli C;Madeddu P
通讯作者：
Madeddu P
影响因子：
11.4
作者：
Ema, M;Hirota, K;Fujii-Kuriyama, Y
通讯作者：
Fujii-Kuriyama, Y
影响因子：
6.1
作者：
Hamada, Yasuhiro;Miyata, Satoshi;Kasuga, Masato
通讯作者：
Kasuga, Masato
DOI：
10.2174/187152908786786179
发表时间：
2008-12-01
影响因子：
--
作者：
Billiet, Ludivine;Rouis, Mustapha
通讯作者：
Rouis, Mustapha