Apoptosis Signal-Regulating Kinase 1 Inhibition in Pulmonary Hypertension. Too Much to ASK?

Inhibition of p38 reduces the proliferation and migration of pulmonary artery fibroblasts and cytokine release from these cells in vitro (3-5), all of which are key elements of pulmonary vascular remodeling. The main criticisms of preclinical studies focus on the fidelity of animal models with regar...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2018-02, Vol.197 (3), p.286-288
Main Author: Wilkins, Martin R
Format: Article
Language:English
Subjects:
Apoptosis
Clinical trials
Disease Progression
Drugs
Fibroblasts
Humans
Hypertension, Pulmonary
Hypoxia
Kinases
MAP Kinase Kinase Kinase 5
Pathology
Patients
Phosphorylation
Proteins
Pulmonary arteries
Pulmonary hypertension
Rodents
Signal Transduction
Veins & arteries
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Summary:Inhibition of p38 reduces the proliferation and migration of pulmonary artery fibroblasts and cytokine release from these cells in vitro (3-5), all of which are key elements of pulmonary vascular remodeling. The main criticisms of preclinical studies focus on the fidelity of animal models with regard to disease in humans, and the failure to apply the same methodological rigor required in clinical studies (specifically, blinding, randomization, and a priori sample size calculations). Welsh DJ, Peacock AJ, MacLean M, Harnett M. Chronic hypoxia induces constitutive p38 mitogen-activated protein kinase activity that correlates with enhanced cellular proliferation in fibroblasts from rat pulmonary but not systemic arteries.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201709-1814ed