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<p>Tenascin-X (Tnxb) is a large extracellular matrix protein that has been associated with atherosclerosis. The objective of this study was to investigate the effect of <i>Tnxb</i> and its contribution to recovery after myocardial ischemia/reperfusion (I/R) injury. Tnxb expression was reduced in ECs of mice with ligation of the left anterior descending. Conditional <i>Tnxb</i> overexpression using adeno-associated viruses promoted Akt phosphorylation and mitigated myocardial injury and cardiac dysfunction in mice with myocardial I/R. Furthermore, overexpression of <i>Tnxb</i> alleviated apoptosis and enhanced angiogenesis in vivo and in vitro. Krueppel-like factor 4 (Klf4) recruited SWItch/sucrose nonfermentable (SWI/SNF) to the distal enhancer of <i>Tnxb</i> to transcriptionally activate <i>Tnxb</i>, thereby promoting Akt phosphorylation. The mitigating effect of <i>Klf4</i> overexpression on I/R-induced endothelial apoptosis and angiogenic dysfunction was dependent on <i>Tnxb</i> activation, since <i>Tnxb</i> knockdown reversed the effects of <i>Klf4</i> overexpression on myocardial I/R injury. In summary, we show that Klf4 recruits SWI/SNF to the distal enhancer of <i>Tnxb</i> to transcriptionally activate <i>Tnxb</i>, which promotes Akt phosphorylation and alleviates myocardial I/R-induced endothelial apoptosis and angiogenic dysfunction. Lastly, Tnxb was identified as a potential therapeutic target in EC injuries induced by myocardial I/R.</p> Graphical Abstract <p>The image(s) herein have been obtained from Servier Medical Art (<a href="https://smart.servier.com">https://smart.servier.com</a>), which is licensed under CC BY 4.0 (<a href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</a>).</p> <p></p>

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Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice

  • 期刊论文

  • 发表日期：

    2026年7月23日

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  • Haohao Hao,
  • Xiaolin Zi,
  • Yunhao Jiang,
  • Jiawen Li

摘要

Tenascin-X (Tnxb) is a large extracellular matrix protein that has been associated with atherosclerosis. The objective of this study was to investigate the effect of Tnxb and its contribution to recovery after myocardial ischemia/reperfusion (I/R) injury. Tnxb expression was reduced in ECs of mice with ligation of the left anterior descending. Conditional Tnxb overexpression using adeno-associated viruses promoted Akt phosphorylation and mitigated myocardial injury and cardiac dysfunction in mice with myocardial I/R. Furthermore, overexpression of Tnxb alleviated apoptosis and enhanced angiogenesis in vivo and in vitro. Krueppel-like factor 4 (Klf4) recruited SWItch/sucrose nonfermentable (SWI/SNF) to the distal enhancer of Tnxb to transcriptionally activate Tnxb, thereby promoting Akt phosphorylation. The mitigating effect of Klf4 overexpression on I/R-induced endothelial apoptosis and angiogenic dysfunction was dependent on Tnxb activation, since Tnxb knockdown reversed the effects of Klf4 overexpression on myocardial I/R injury. In summary, we show that Klf4 recruits SWI/SNF to the distal enhancer of Tnxb to transcriptionally activate Tnxb, which promotes Akt phosphorylation and alleviates myocardial I/R-induced endothelial apoptosis and angiogenic dysfunction. Lastly, Tnxb was identified as a potential therapeutic target in EC injuries induced by myocardial I/R.

Graphical Abstract

The image(s) herein have been obtained from Servier Medical Art (https://smart.servier.com), which is licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).