Phosphatase PTEN is critically involved in post-myocardial infarction remodeling through the Akt/interleukin-10 signaling pathway.
Phosphatase PTEN is critically involved in post-myocardial infarction remodeling through the Akt/interleukin-10 signaling pathway.
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DOI：
10.1007/s00395-012-0248-6
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发表时间：
2012-03
影响因子：
9.5
通讯作者：
Cai ZP
中科院分区：
文献类型：
--
作者：
Parajuli N;Yuan Y;Zheng X;Bedja D;Cai ZP
炎性细胞因子白细胞介素（IL）-10和肿瘤坏死因子（TNF）-α在心肌梗死（MI）后左室重构中起重要作用。第十号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）使蛋白激酶Akt失活并促进心脏细胞死亡。然而，目前尚不清楚PTEN是否通过调节IL-10和TNF-α促进MI后重塑。在野生型（WT）小鼠和Pten杂合突变型（HET）小鼠中诱导MI。将Pten腺病毒（adPten）或空载体（adNull）注射到WT小鼠的梗塞周围区域。与WT小鼠相比，HET小鼠的LV扩张减弱，缩短分数增加。adPten小鼠的存活率和缩短率较adPten小鼠降低。在HET小鼠中，梗死周围区域的白细胞浸润减弱，在adPten小鼠中恶化。在WT小鼠的梗死心脏中，PTEN表达上调。HET小鼠心肌梗死后，部分失活的PTEN可增加IL-10的产生，降低TNF-α和基质金属蛋白酶（MMP）-2和-9的表达。而在梗死心脏中，PTEN过表达则产生相反的作用。此外，在HET小鼠的梗死心脏中，Akt抑制降低了Stat 3磷酸化和IL-10表达，而IL-10受体的阻断增加了TNF-α和MMP-2的表达。Akt抑制和IL-10受体阻断均消除了HET小鼠中MI后重塑的衰减。总之，PTEN通过Akt/IL-10信号通路在MI后重构中起关键作用。因此，靶向PTEN可能是心肌梗死后重构的有效途径。
The inflammatory cytokines interleukin (IL)-10 and tumor necrosis factor (TNF)-α play an important role in left ventricular (LV) remodeling after myocardial infarction (MI). Phosphatase and tensin homologue deleted on chromosome ten (PTEN) inactivates protein kinase Akt and promotes cell death in the heart. However, it is not known whether PTEN promotes post-MI remodeling by regulating IL-10 and TNF-α. MI was induced in wildtype (WT) mice and Pten heterozygous mutant (HET) mice. Pten adenoviruses (adPten) or empty vectors (adNull) were injected into the peri-infarct area of WT mice. LV dilation was attenuated and fractional shortening was increased in HET mice compared with WT mice. Survival rate and fractional shortening were decreased in adPten mice compared with adNull mice. Leukocyte infiltration into the peri-infarct area was attenuated in HET mice and worsened in adPten mice. PTEN expression was upregulated in the infarcted heart of WT mice. Partial inactivation of PTEN increased production of IL-10 and decreased expression of TNF-α and matrix metalloproteinase (MMP)-2 and -9 after MI in HET mice. PTEN overexpression caused opposite effects in the infarcted heart. Moreover, in the infarcted heart of HET mice, Akt inhibition decreased Stat3 phosphorylation and IL-10 expression, and blockade of the IL-10 receptor increased TNF-α and MMP-2 expression. Both Akt inhibition and IL-10 receptor blockade abolished the attenuation of post-MI remodeling in HET mice. In conclusion, PTEN is critically involved in post-MI remodeling through the Akt/IL-10 signaling pathway. Therefore, targeting PTEN may be an effective approach to post-MI remodeling.
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影响因子：
10.8
作者：
Oudit, Gavin Y.;Kassiri, Zamaneh;Penninger, Josef M.
通讯作者：
Penninger, Josef M.
DOI：
10.1152/ajpheart.00915.2009
发表时间：
2010-04-01
影响因子：
4.8
作者：
Keyes, Kyle T.;Xu, Jing;Ye, Yumei
通讯作者：
Ye, Yumei
影响因子：
9.5
作者：
Hua, Yinan;Zhang, Yingmei;Ren, Jun
通讯作者：
Ren, Jun
影响因子：
20.1
作者：
Burchfield, Jana S.;Iwasaki, Masayoshi;Dimmeler, Stefanie
通讯作者：
Dimmeler, Stefanie
影响因子：
20.1
作者：
Krishnamurthy P;Rajasingh J;Lambers E;Qin G;Losordo DW;Kishore R
通讯作者：
Kishore R