Research ArticlePulmonary Arterial Hypertension

Cellular senescence impairs the reversibility of pulmonary arterial hypertension

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Science Translational Medicine  29 Jul 2020:
Vol. 12, Issue 554, eaaw4974
DOI: 10.1126/scitranslmed.aaw4974

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Reversing maladaptive remodeling

Pathologic vascular remodeling of pulmonary arterial hypertension (PAH) associated with congenital heart disease in children can be reversed by shunt closure, which induces hemodynamic unloading, up to a point in time, but mechanisms driving the transition from reversible to irreversible vasculopathy remain poorly defined. Van der Feen et al. used a rodent model of monocrotaline- and aortocaval shunt–induced pulmonary hypertension with lung transplant to study the time course of reversibility of vascular remodeling. They demonstrated that cellular senescence was associated with late-stage, irreversible PAH and treatment with a senolytic could alter maladaptive vascular remodeling, suggesting a potential therapeutic target for patients with PAH.

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