Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.
H, H., X, Z., Y, J., & J, L. (2026). Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.. Cardiovascular toxicology. https://doi.org/10.1007/s12012-026-10158-z
H H, X Z, Y J, J L. Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.. Cardiovascular toxicology. 2026; doi: 10.1007/s12012-026-10158-z
H H, X Z, Y J, et al. Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.[J]. Cardiovascular toxicology. 2026. DOI: 10.1007/s12012-026-10158-z.
@article{h2026,
author = {Hao H and Zi X and Jiang Y and Li J},
title = {Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice.},
journal = {Cardiovascular toxicology},
year = {2026},
doi = {10.1007/s12012-026-10158-z},
note = {PMID: 42490037},
}
TY - JOUR AU - Hao H AU - Zi X AU - Jiang Y AU - Li J TI - Tnxb Alleviates Myocardial Ischemia-Reperfusion Injury Through Facilitating Akt-Dependent Endothelial Cell Survival and Angiogenesis in Mice. T2 - Cardiovascular toxicology PY - 2026 DO - 10.1007/s12012-026-10158-z AN - PMID:42490037 ER -
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.