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12.04.2021 | Original Article

An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-Induced Drug Resistance to Enhance the Efficacy of Myocardial Protection

verfasst von: Wen Zhou, Bin Zhang, Keyu Fan, Xiaojian Yin, Jinfeng Liu, Shaohua Gou

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 4/2022

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Abstract

Purpose

Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia-induced drug resistance.

Methods

In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown, and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.

Results

Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.

Conclusion

Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.
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Metadaten
Titel
An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-Induced Drug Resistance to Enhance the Efficacy of Myocardial Protection
verfasst von
Wen Zhou
Bin Zhang
Keyu Fan
Xiaojian Yin
Jinfeng Liu
Shaohua Gou
Publikationsdatum
12.04.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 4/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07182-2

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