The reversal of pulmonary vascular remodeling through inhibition of p38 MAPK-alpha: a potential novel anti-inflammatory strategy in pulmonary hypertension.
Bottom Line: Previous in vitro studies suggest p38 MAPKα is critical in the proliferation of pulmonary artery fibroblasts, an important step in the pathogenesis of pulmonary vascular remodeling (PVremod).Increased expression of phosphorylated p38 MAPK and p38 MAPKα was observed in the pulmonary vasculature from patients with idiopathic pulmonary arterial hypertension, suggesting a role for activation of this pathway in the PVremod A reduction of IL-6 levels in serum and lung tissue was found in the drug-treated animals, suggesting a potential mechanism for this reversal in PVremod.This study suggests that the p38 MAPK and the α-isoform plays a pathogenic role in both human disease and rodent models of pulmonary hypertension potentially mediated through IL-6.
Affiliation: Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, United Kingdom; firstname.lastname@example.org.Show MeSH
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Mentions: Our group and others have shown previously that fibroblasts isolated from chronic hypoxic animals have undergone a phenotypic switch, which results in constitutive activation of p38 MAPK and a proproliferative phenotype. Whether this effect is seen in other models of pulmonary hypertension is unknown. Therefore, we examined the proliferative potential of fibroblasts derived from MCT animals and compared them to that of fibroblasts isolated from both normal and chronic hypoxic animals (Fig. 1A). This clearly showed an increased predisposition to proliferation by the MCT-derived fibroblasts in relation to low dose serum stimulation. The effect was lost at 5% serum stimulation, which may reflect cell contact inhibition.
Affiliation: Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, United Kingdom; email@example.com.