mTOR: A Key to Both Pulmonary Vessel Remodeling and Right Ventricular Function in Pulmonary Arterial Hypertension?

Right ventricular (RV) failure is the ultimate cause of death in patients with severe pulmonary arterial hypertension (PAH). RV dysfunction has long been ascribed primarily to an increase in the RV afterload, and treatments to diminish pulmonary vascular resistance were therefore considered key to improving RV function. However, progressive RV dysfunction despite improvements in pulmonary hemodynamics was reported recently in some patients. Moreover, differences in the severity of RV dysfunction have been demonstrated across patients with similar pulmonary hemodynamics. For instance, among patients with similar hemodynamics, those with idiopathic PAH usually have better RV function than those with systemic sclerosis, and the prognosis also differs between these two PAH etiologies. A limitation of this study is the issue of whether the model used by Pena and colleagues is suitable for investigating RV dysfunction. Translating data from experimental PAH models into human applications is difficult given the differences in disease progression and cardiac consequences, which unfold over years in humans and weeks in murine models.