Inflammatory Response of Pulmonary Artery Smooth Muscle Cells Exposed to Oxidative and Biophysical Stress

Abstract

Pulmonary hypertension in the neonate requires treatment with oxygen and positive pressure ventilation, both known to induce lung injury. The direct response of pulmonary artery smooth muscle cells, the most abundant cells in the artery wall, to the stress of positive pressure and hyperoxia has not been previously studied. Pulmonary artery smooth muscle cells were cultured in temperature- and pressure-controlled air-tight chambers under conditions of positive pressure or hyperoxia for 24 h. Control cells were cultured in room air under atmospheric pressure. After the exposure period, culture medium was collected and samples were analyzed by ELISA, Human Cytokine 25-Plex Panel using a Luminex 200 analyzer and Western blot. Secretion of various inflammatory mediators, specifically IL-6, IL-8, IL-2R, MIP-1β, MCP-1, IP-10, IL-7, IL-1RA, and IFN-α, was higher in the positive pressure and hyperoxia groups compared with control. The level of cyclin D1 was decreased in the hyperoxia and positive pressure group compared with control. Levels of fibronectin and α-smooth muscle actin were not different among the groups. Pulmonary artery smooth muscle cells directly produce multiple inflammatory mediators in response to oxidative and biophysical stress in vitro, which may be part of a cascade that leads to the vascular and perivascular changes in pulmonary hypertension.

Prenatal treatment with rosiglitazone attenuates vascular remodeling and pulmonary monocyte influx in experimental congenital diaphragmatic hernia

“…MCP-1 is produced by alveolar epithelial, endothelial, SMCs, and monocytes/macrophages after exposition with acute phase proteins, bacterial or viral products [ 26 , 31 ]. The activation of perivascular monocytes/macrophages by increased MCP-1 expression has been shown to result in endothelial dysfunction and SMC proliferation.…”

The role of chemokines and chemokine receptors in pulmonary arterial hypertension

“…PASMCs increase CXCL8 expression in response to mechanical stress (Costa et al, 2018). Broiler chickens, which develop spontaneous PAH with plexiform-like lesions, display decreased expression of CXCL8 compared to layer chickens which are resistant to PAH (Tan, Shao, Fan, & Ying, 2018).…”

“…Hypoxia induces CXCL8 expression in PASMCs (Li et al, 2017), while only the combination of hypoxia and expression of high mobility group box protein 1 (HMGB1) increases CXCL8 expression in PAECs (Li et al, 2017). PASMCs increase CXCL8 expression in response to mechanical stress (Costa et al, 2018). Broiler chickens, which develop spontaneous PAH with plexiform‐like lesions, display decreased expression of CXCL8 compared to layer chickens which are resistant to PAH (Tan, Shao, Fan, & Ying, 2018).…”

Association of plasma adiponectin with pulmonary hypertension, mortality and heart failure in African Americans: Jackson Heart Study

“…Adiponectin is a polypeptide hormone secreted by adipocytes that is involved in multiple pathways of inflammatory, hormonal, thrombotic and metabolic signaling and has been identified as a modulator of vascular remodeling. 1 – 9 These pathophysiological mechanisms and pathways are important in the development of pulmonary vascular disease and suggest a possible relationship between the adipose tissue and pulmonary vascular health. Basic science and in vivo studies have shown beneficial effects of adiponectin on low grade inflammation, oxidative stress and apoptosis, underscoring an important role for adiponectin as a protective adipokine in cardiovascular and vascular function.…”