Abstract
Background: It is well established that subtypes of pulmonary hypertension are associated with a range of haemolytic anaemias; more recently it has been suggested that subclinical haemolysis may be common more generally in pulmonary arterial hypertension (PAH) and associated with disease pathogenesis.
Aims: To investigate whether specific cellular stress responses are associated with exposure to cell free haemoglobin.
Methods: Study endpoints were focused on the determination of overall cellular reactive oxygen species (ROS) and mitochondrial ROS production. Pulmonary artery endothelial cells (PAECs) were treated with 10 µM of methaemoglobin (metHb) for 24 hours. Following treatment, overall cellular ROS and mitochondrial ROS were measured by flow cytometry. PAECs were also treated with 1 µM, 3 µM and 10 µM of metHb for 24h; cellular proliferation and the release of pro-inflammatory cytokines were analysed by the BrdU assay and ELISA, respectively.
Results: The overall endothelial ROS (*p<0.05) and the cellular mitochondrial ROS were found to be increased when treated with metHb. Treatment also increased PAECs proliferation (***p<0.0001) and the release of IL-6 pro-inflammatory cytokines (*p<0.05).
Conclusions: These findings reveal a strong relationship between metHb-induced oxidative damage and further enhancement of endothelial dysfunction through overproduction of cellular ROS. Targeting this pathway will be essential to further understand the potentially novel cellular mechanisms involved.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5042.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019