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; email@example.com.Show MeSH
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Mentions: Animals were exposed to hypoxia for a period of 2 wk and then treated with daily intraperitoneal injections of SB203580 or vehicle for a further 2 wk while remaining in hypoxia. There was a significant reduction in the RVSP in the drug-treated group compared with the vehicle-treated group at 4 wk and control hypoxic animals after 2 wk (Fig. 4A), with almost full reversal to that of normal animals.
Affiliation: Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, United Kingdom; firstname.lastname@example.org.