An Orally Active TRPV4 Channel Blocker Prevents and Resolves Pulmonary Edema Induced by Heart Failure
Abstract
Transient receptor potential vanilloid 4 (TRPV4) channels are expressed in human heart failure lungs, which can be blocked to prevent and resolve heart failure–induced pulmonary edema.
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HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature.
“HUVECs may not entirely recapitulate all known roles for TRPV4 in tumor vasculature. 24,28,35,51,53,66”
From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [28]
Using simple, direct modulation of TRPV4 with GSK101 in a 3D microfluidic system, vascular integrity can be tuned to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, and achieve vascular leakiness comparable with previous MTM studies using tumor cells.
“Using this simple, direct modulation of TRPV4 with GSK101 in a 3D micro fl uidic system, we can therefore tune the vascular integrity to recapitulate known TRPV4 physiological functions in vivo, especially in pulmonary edema, 28,30,51,52 and achieve vascular leakiness in a manner that is comparable with previous MTM studies using tumor cells. 2,53”
From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [28]
Cites
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Bhatia, S. N., & Ingber, D. E. (2014) · Nature Biotechnology · doi:10.1038/nbt.2989 · Cited by 3,305 · see citing works
Organs-on-chips at the frontiers of drug discovery
Esch, E. W., Bahinski, A., & Huh, D. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4539 · Cited by 1,185 · see citing works
A Human Disease Model of Drug Toxicity–Induced Pulmonary Edema in a Lung-on-a-Chip Microdevice
Huh, D., Leslie, D. C., Matthews, B. D., Fraser, J. P., Jurek, S., Hamilton, G. A., Thorneloe, K. S., McAlexander, M. A., & Ingber, D. E. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004249 · Cited by 993 · see citing works
Self-citationTRPV4: molecular conductor of a diverse orchestra
White, J. P. M., Cibelli, M., Urban, L., Nilius, B., McGeown, J. G., & Nagy, I. (2016) · Physiological Reviews · doi:10.1152/physrev.00016.2015 · Cited by 405 · see citing works
TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice
Rahaman, S. O., Grove, L. M., Paruchuri, S., Southern, B. D., Abraham, S., Niese, K. A., Scheraga, R. G., Ghosh, S., Thodeti, C. K., Zhang, D. X., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci75331 · Cited by 310 · see citing works
Davis, M. J., Earley, S., Li, Y.-S., & Chien, S. (2023) · Physiological Reviews · doi:10.1152/physrev.00053.2021 · Cited by 273 · see citing works
TRPV4 plays a role in matrix stiffness-induced macrophage polarization
Dutta, B., Goswami, R., & Rahaman, S. O. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.570195 · Cited by 124 · see citing works
Causes and treatment of oedema in patients with heart failure
Clark, A. L., & Cleland, J. G. F. (2013) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2012.191 · Cited by 112 · see citing works
TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation
Sharma, S., Goswami, R., Merth, M., Cohen, J., Lei, K. Y., Zhang, D. X., & Rahaman, S. O. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00187.2016 · Cited by 90 · see citing works
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Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model
Vu, M. N., Rajasekhar, P., Poole, D. P., Khor, S. Y., Truong, N. P., Nowell, C. J., Quinn, J. F., Whittaker, M., Veldhuis, N. A., & Davis, T. P. (2019) · ACS Applied Nano Materials · doi:10.1021/acsanm.8b02056 · Cited by 52 · see citing works
- Authors
- Thorneloe, K. S., Cheung, M., Bao, W., Alsaid, H., Lenhard, S., Jian, M.-Y., Costell, M., Maniscalco-Hauk, K., Krawiec, J. A., Olzinski, A., Gordon, E., Lozinskaya, I., Elefante, L., Qin, P., Matasic, D. S., James, C., Tunstead, J., Donovan, B., Kallal, L., Waszkiewicz, A., Vaidya, K., Davenport, E. A., Larkin, J., Burgert, M., Casillas, L. N., Marquis, R. W., Ye, G., Eidam, H. S., Goodman, K. B., Toomey, J. R., Roethke, T. J., Jucker, B. M., Schnackenberg, C. G., Townsley, M. I., Lepore, J. J., & Willette, R. N.
- Affiliations
- GlaxoSmithKline (United States) (US)
- University of South Alabama (US)
- Heart Failure Discovery Performance Unit, Metabolic Pathways and Cardiovascular Therapy Area Unit, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
- Corresponding author
- Thorneloe, Kevin S.
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2012-11-07
- Volume
- 4
- Issue
- 159
- Pages
- 159ra148-159ra148
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2165344509
- Cited by
- 337
- References
- 3
- Citations by year
- 2026: 20 · 2025: 17 · 2024: 19 · 2023: 19 · 2022: 24 · 2021: 33 · 2020: 40 · 2019: 26 · 2018: 23 · 2017: 25 · 2016: 21 · 2015: 27 · 2014: 27 · 2013: 14 · 2012: 2
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Takotsubo Cardiomyopathy and Associated Phenomena
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- TRPV4 channel, GSK2193874, pulmonary edema, heart failure, pulmonary venous pressure, pulmonary capillary endothelium, vascular permeability, myocardial infarction, arterial oxygenation, small molecule drugs
- MeSH terms
- Administration, Oral, Animals, Blood Pressure, Calcium, Disease Models, Animal, Diuretics, Endothelium, Heart Failure, Heart Rate, Humans, Lung, Permeability, Pulmonary Edema, Water-Electrolyte Balance, Ion Channel Gating, Mice, Knockout, Protein Transport, Membrane Transport Modulators, TRPV Cation Channels, Mice, Rats, In Vitro Techniques
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