The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

Schwingshackl, Andreas

doi:10.1152/ajplung.00458.2015

Cited by 28 publications

(22 citation statements)

References 227 publications

(236 reference statements)

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“…There is a large variety of cell structures that may act as mechanosensors. The plasma membrane has force-sensing ion channels (24), and the cytoskeleton can trigger intracellular signaling cascades (25). Moreover, the cytoskeleton may transmit the forces from the extracellular matrix to different organelles such as mitochondria or the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

et al. 2018

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The nuclear membrane acts as a mechanosensor that drives cellular responses following changes in the extracellular environment. Mechanically ventilated lungs are exposed to an abnormally high mechanical load that may result in clinically relevant alveolar damage. We report that mechanical ventilation in mice increased the expression of Lamin-A, a major determinant of nuclear membrane stiffness, in alveolar epithelial cells. Lamin-A expression increased and nuclear membrane compliance decreased in human bronchial epithelial cells after a mechanical stretch stimulus and in a murine model of lung injury after positive-pressure ventilation. Reducing Lamin-A maturation by depletion of the protease-encoding gene preserved alveolar nuclear membrane compliance after mechanical ventilation in mice. Ventilator-induced proapoptotic gene expression changes and lung injury were reduced in mice lacking compared to wild-type control animals. Similarly, treatment with the human immunodeficiency virus protease inhibitors lopinavir and ritonavir reduced the accumulation of Lamin-A at nuclear membranes and preserved nuclear membrane compliance after mechanical ventilation, mimicking the protective phenotype of animals. These results show that the pathophysiological response to lung mechanical stretch is sensed by the nuclear membranes of lung alveolar cells, and suggest that protease inhibitors might be effective in preventing ventilator-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

et al. 2018

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“…After decades of research, it has been proved that the activity of ion channel changed quickly in response to mechanical stress and contributed to vascular hyperpermeability. [ 42 ]…”

Section: Olecular M Echanisms Of mentioning

confidence: 99%

Molecular Mechanisms of Ventilator-Induced Lung Injury

Chen

Xia

Shang

et al. 2018

Chinese Medical Journal

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Objective:Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.Data Sources:This review was based on articles in the PubMed database up to December 2017 using the following keywords: “ventilator-induced lung injury”, “pathogenesis”, “mechanism”, and “biotrauma”.Study Selection:Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.Results:The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.Conclusions:Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.

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“…Nach heutiger Vorstellung werden mechanische Reize zum einen über Integrine (spezielle Transmembranproteine) direkt von der Extrazellulärmatrix der Lunge auf verschiedene Zellenwie Alveolarepithelzellen, Alveolarmakrophagen, Gefäßendothelzellen und Fibroblastenübertragen [6]. Zum anderen kommt es infolge von mechanischen Reizen zur Aktivierung von Ionenkanälen mit einem vermehrten Kalzium-und Kaliumeinstrom in die Zellen [7]. Letztlich wird so die Transkription verschiedener Zytokine und Inflammationsmediatoren initiiert.…”

Section: Remote Organ Failureunclassified

ARDS – Ein Update – Teil 2: Therapie und Outcome

Dembinski¹,

Mielck²

2018

Anästhesiol Intensivmed Notfallmed Schmerzther

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The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure due to inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of scientific research numerous issues especially regarding mechanical ventilation as the most important treatment option remain unclear. Most important, adjustment of mechanical ventilation is challenging due to desirable beneficial effects on pulmonary gas exchange on the one hand and deleterious effects in terms of ventilator-associated lung injury on the other. Specifically, optimal settings of positive end-expiratory pressure and the role of spontaneous breathing activity are still controversial. Because no specific pharmacological therapy revealed beneficial effects until today, adjunctive treatment is actually limited to prone positioning and restrictive fluid balance. Long-term outcome of ARDS survivors is often affected by anxiety and mental health disorders.

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The role of stretch-activated ion channels in acute respiratory distress syndrome: finally a new target?

Cited by 28 publications

References 227 publications

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

Preventing loss of mechanosensation by the nuclear membranes of alveolar cells reduces lung injury in mice during mechanical ventilation

Molecular Mechanisms of Ventilator-Induced Lung Injury

ARDS – Ein Update – Teil 2: Therapie und Outcome

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