Inhibition of transient receptor potential vanilloid 4: A promising novel strategy for myocardial ischemia/reperfusion injury treatment
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Abstract
Myocardial ischemia-reperfusion (IR) injury remains a major clinical challenge, often exacerbating cardiac damage despite timely reperfusion. The transient receptor potential vanilloid 4 (TRPV4), a Ca²⁺-permeable non-selective cation channel, has emerged as a key mediator of IR injury. TRPV4 is widely expressed in cardiomyocytes, endothelial cells, and immune cells, and its activation under ischemic stress promotes Ca²⁺ overload, oxidative stress, inflammation, and endothelial dysfunction. Upregulation and membrane translocation of TRPV4 during IR aggravates intracellular Ca²⁺ influx, sarcoplasmic reticulum Ca²⁺ leak, and mitochondrial impairment. TRPV4 also amplifies reactive oxygen species (ROS) production, impairs antioxidant defenses, and triggers inflammatory signaling. Additionally, TRPV4 contributes to cardiomyocyte apoptosis, pyroptosis, and possibly ferroptosis. Preclinical studies demonstrate that selective TRPV4 antagonists (e.g., HC-067047, GSK2193874) significantly reduce infarct size, preserve cardiac function, suppress arrhythmias, alleviate myocardial stunning, and prevent coronary no-reflow. The age-related upregulation of TRPV4 further highlights its therapeutic relevance in elderly patients. Targeting TRPV4 thus represents a promising strategy to mitigate multifactorial myocardial injury and improve outcomes following reperfusion therapy.
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Self-citationMartinez‐Navarro, H., Zhou, X., & Rodríguez, B. (2024) · Annual Review of Physiology · doi:10.1146/annurev-physiol-042022-020541 · Cited by 12 · see citing works
Li, X., Lu, K., Guo, S., Xue, S., & Feng, L. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.110973 · Cited by 11 · see citing works
Gao, M., Zhang, P., Han, J. D. J., Tang, C., Zhu, Y., Kan, H., Li, H., Han, X., & Ma, X. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00780-8 · Cited by 7 · see citing works
TAX1BP3 Causes TRPV4-Mediated Autosomal Recessive Arrhythmogenic Cardiomyopathy
Perelli, R. M., Dewars, E. R., Cope, H., Behura, A. S., Ponek, A., Sala, A. M., Zhang, Z., Muralidharan, P., Moya‐Mendez, M. E., Berkman, A. M., et al. (2025) · Circulation Research · doi:10.1161/circresaha.124.325180 · Cited by 5 · see citing works
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Li, P., Zhang, Y., Guo, S., Hu, H., Cheng, T., Zeng, K., Zhang, T., Zhong, L., Lin, J., & Sun, B. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02311-5 · Cited by 1 · see citing works
Huang, L., Liu, W., Li, Z., Wang, Z., Li, X., & Wu, Y. (2026) · Natural Product Research · doi:10.1080/14786419.2026.2709594
Self-citationItching, Ionic Channels, Immune System, Magnesium and Antioxidants
Sastre, M. C., Soler, J. M., & Umbert, I. J. (2026) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s614123
Soft tissue mechanosensing and remodeling: the core regulatory role of Piezo/TRPV4 ion channels
Fan, X., Shi, M., Wang, Z., Zhao, C., Zhao, Y., Zhou, Y., & Xu, H. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1869360
Self-citationYang, J., Li, J., Li, G., Zhong, H., Yang, H., Zhong, K., Wang, F., Huang, Z., Huang, D., Wei, W., et al. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1945533
- Authors
- Dong, Q., Wang, Z., Wu, Q., & Du, Y.
- Affiliations
- Wuhan Union Hospital (CN)
- Corresponding author
- Wu, Qiongfeng
- Du, Yimei
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2025-12
- Volume
- 193
- Pages
- 118765
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W4416168586
- Cited by
- 4
- References
- 89
- Citations by year
- 2026: 4
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82470328, 82170326, 82100339)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Keywords
- TRPV4, transient receptor potential vanilloid 4, myocardial ischemia-reperfusion injury, TRPV4 antagonist, calcium overload, oxidative stress, inflammation, cardiomyocyte apoptosis, pyroptosis, ferroptosis, myocardial stunning, infarct size, reperfusion therapy
- MeSH terms
- Animals, Humans, Myocardial Reperfusion Injury, Oxidative Stress, TRPV Cation Channels
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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