Effects of Hyperoxia and Hyperoxic Oscillations on the Proteome of Murine Lung Microvascular Endothelium.
Akos TiboldiEva Hunyadi-GulyasPeter WohlrabJohannes A SchmidKlaus MarkstallerKlaus Ulrich KleinVerena TretterPublished in: Antioxidants (Basel, Switzerland) (2022)
Patients presenting with insufficient tissue oxygenation and impaired lung function as in acute respiratory distress syndrome (ARDS) frequently require mechanical ventilation with supplemental oxygen. Despite the lung being used to experiencing the highest partial pressure of oxygen during healthy breathing, the organ is susceptible to oxygen-induced injury at supraphysiological concentrations. Hyperoxia-induced lung injury (HALI) has been regarded as a second hit to pre-existing lung injury and ventilator-induced lung injury (VILI) attributed to oxidative stress. The injured lung has a tendency to form atelectasis, a cyclic collapse and reopening of alveoli. The affected lung areas experience oxygen conditions that oscillate between hyperoxia and hypoxia rather than remaining in a constant hyperoxic state. Mechanisms of HALI have been investigated in many animal models previously. These studies provided insights into the effects of hyperoxia on the whole organism. However, cell type-specific responses have not been dissected in detail, but are necessary for a complete mechanistic understanding of ongoing pathological processes. In our study, we investigated the effects of constant and intermittent hyperoxia on the lung endothelium from a mouse by an in vitro proteomic approach. We demonstrate that these oxygen conditions have characteristic effects on the pulmonary endothelial proteome that underlie the physiological (patho)mechanisms.
Keyphrases
- acute respiratory distress syndrome
- mechanical ventilation
- extracorporeal membrane oxygenation
- diabetic rats
- oxidative stress
- lung function
- high glucose
- intensive care unit
- endothelial cells
- nitric oxide
- cystic fibrosis
- pulmonary hypertension
- drug induced
- respiratory failure
- signaling pathway
- dna damage
- atomic force microscopy
- single molecule
- stress induced
- label free