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: Immunohistochemical staining of sections from the lungs of patients with IPAH who had undergone transplantation showed increased phospho-p38 MAPK expression compared with control lungs (Fig. 8A). This is shown in all layers of the vascular wall (Fig. 8B). There was increased staining for p38 MAPKα, which was mainly in a nuclear distribution in the control vessels but involved both nuclear and cytoplasmic staining in the IPAH patients (Fig. 8, C and D). This was again demonstrated in all the layers of the vascular wall (Fig. 8E). With the use of an intensity scoring technique, there was higher expression demonstrated for p38 MAPKα in the vessels of patients with IPAH compared with controls (Fig. 8F) (1).
Affiliation: Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, United Kingdom; email@example.com.