American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2018
Comparative StudyASK1 Inhibition Halts Disease Progression in Preclinical Models of Pulmonary Arterial Hypertension.
Progression of pulmonary arterial hypertension (PAH) is associated with pathological remodeling of the pulmonary vasculature and the right ventricle (RV). Oxidative stress drives the remodeling process through activation of MAPKs (mitogen-activated protein kinases), which stimulate apoptosis, inflammation, and fibrosis. ⋯ ASK1 inhibition reduced pathological remodeling of the pulmonary vasculature and the right ventricle and halted progression of pulmonary hypertension in rodent models. These preclinical data inform the first description of a causal role of ASK1 in PAH disease pathogenesis.