Stiftung Tierärztliche Hochschule Hannover (TiHo)

Aspirin enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways

Zhang, Xiaohui; Chen, Bixia; Wu, Jiaxin; Sha, Junzhou; Yang, Bo; Zhu, Jie; Sun, Jiarui; Hartung, Jörg GND; Bao, Endong

Heat stress (HS) often causes sudden death of humans and animals due to heart failure, mainly resulting from the contraction of cardiac microvasculature followed by myocardial ischemia. Cardiac microvascular endothelial cells (CMVECs) play an important role in maintaining vasodilatation. Aspirin (ASA) is well known for its protective abilities of febrile animals. However, there is little knowledge about molecular resistance mechanisms of CMVECs and which role ASA may play in this context. Therefore, we used a heat stress model of rat cardiac microvascular endothelial cell cultures in vitro and investigated the cell injuries and molecular resistance mechanism of CMVECs caused by heat stress, and the effect of aspirin (ASA) on it. HS induced severe pathological damage of CMVECs and cellular oxidative stress and dysfunction of NO release. Hsp90 was proven to be indispensable for resisting HS-injury of CMVECs through PI3K-Akt and PKM2 signaling pathways. Meanwhile, PKM2 functioned in reducing Akt phosphorylation. ASA treatment of CMVECs induced a significant expression of Hsp90, which promoted both Akt and PKM2 signals, which are beneficial for relieving HS damage and maintaining the function of CMVECs. Akt activation also promoted HSF-1 that regulates the expression of Hsp70, which is known to assist Hsp90's molecular chaperone function and when released to the extracellular liquid to protect myocardial cells from HS damage. To the best of our knowledge, this is the first study to show that HS damages CMVECs and the protection mechanism of Hsp90 on it, and that ASA provides a new potential strategy for regulating cardiac microcirculation preventing HS-induced heart failure.

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Zhang, X., Chen, B., Wu, J., Sha, J., Yang, B., Zhu, J., Sun, J., Hartung, J., Bao, E., 2020. Aspirin enhances the protection of Hsp90 from heat-stressed injury in cardiac microvascular endothelial cells through PI3K-Akt and PKM2 pathways. Cells 9. https://doi.org/10.3390/cells9010243
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