Apelin analog treatment reverses severe pulmonary arterial hypertension and right ventricular heart failure

In this study, a sugen-hypoxia rat model of PAH was used to evaluate a novel, degradation-resistant apelin analog targeting the apelinergic pathway, which is implicated in pulmonary vascular remodeling. Treatment with the apelin analog reversed key pathological features of PAH, including pulmonary vascular lesions, elevated pulmonary arterial pressures, RV dilation and dysfunction, and early cardiorenal syndrome.

The therapy also reduced RV cardiomyocyte and fibroblast activation caused by pressure overload. Single-nucleus RNA sequencing of the lungs and RV demonstrated that apelin analog treatment activated protective molecular programs, notably restoring balance between protective BMPR2 signaling and pathogenic TGFBR2 signaling. Overall, these findings suggest that exogenous apelin therapy may represent a promising strategy to reverse pulmonary vascular and cardiac remodeling in PAH and warrants further clinical investigation.