| Autor: |
Kuebler WM; Institute of Physiology, Charité Medical University of Berlin, Berlin, Germany., Jordt SE; Department of Anesthesiology, Duke University, Durham, North Carolina., Liedtke WB; Department of Anesthesiology, Duke University, Durham, North Carolina.; Department of Neurology, Duke University, Durham, North Carolina.; Department of Neurobiology, Duke University, Durham, North Carolina. |
| Jazyk: |
angličtina |
| Zdroj: |
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2020 Jun 01; Vol. 318 (6), pp. L1239-L1243. Date of Electronic Publication: 2020 May 13. |
| DOI: |
10.1152/ajplung.00161.2020 |
| Abstrakt: |
Lethality of coronavirus disease (COVID-19) during the 2020 pandemic, currently still in the exponentially accelerating phase in most countries, is critically driven by disruption of the alveolo-capillary barrier of the lung, leading to lung edema as a direct consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We argue for inhibition of the transient receptor potential vanilloid 4 (TRPV4) calcium-permeable ion channel as a strategy to address this issue, based on the rationale that TRPV4 inhibition is protective in various preclinical models of lung edema and that TRPV4 hyperactivation potently damages the alveolo-capillary barrier, with lethal outcome. We believe that TRPV4 inhibition has a powerful prospect at protecting this vital barrier in COVID-19 patients, even to rescue a damaged barrier. A clinical trial using a selective TRPV4 inhibitor demonstrated a benign safety profile in healthy volunteers and in patients suffering from cardiogenic lung edema. We argue for expeditious clinical testing of this inhibitor in COVID-19 patients with respiratory malfunction and at risk for lung edema. Perplexingly, among the currently pursued therapeutic strategies against COVID-19, none is designed to directly protect the alveolo-capillary barrier. Successful protection of the alveolo-capillary barrier will not only reduce COVID-19 lethality but will also preempt a distressing healthcare scenario with insufficient capacity to provide ventilator-assisted respiration. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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