# Incomplete reverse remodeling in pulmonary hypertension‐induced right ventricular dysfunction in aged mice

## TL;DR

This study shows that while the right ventricle of aged mice can reverse some structural changes after pulmonary hypertension, its function does not improve.

## Contribution

The study reveals incomplete functional recovery in aged mice after reverse remodeling of the right ventricle.

## Key findings

- RV hypertrophy and fibrosis were reduced after normoxia re-exposure in aged mice.
- RV systolic function, as measured by FAC and SV, remained impaired despite structural improvements.
- Autophagy and anti-fibrotic pathways may contribute to morphological reverse remodeling.

## Abstract

Right ventricular (RV) function is the strongest predictor of survival in pulmonary hypertension (PH) and age‐related heart disease; however, no therapies improve RV function. Understanding how the RV undoes pathological remodeling (reverse remodeling) might aid in identifying therapies, particularly in aging populations in which RV failure is significant. Our objective was to determine if the aged RV can undergo reverse remodeling following the resolution of pathological afterload by pulmonary hypertension (PH). We exposed male and female aged (18–21 months) C57BL/6 mice to hypobaric hypoxia (HH) for 4 weeks to model PH before returning the mice to normoxia for three (WK3RR) or six (WK6RR) weeks. HH stimulated RV hypertrophy and fibrosis which were attenuated with WK3RR and WK6RR. Activation of autophagy and anti‐fibrotic pathways likely underlie morphological reverse remodeling. However, HH decreased RV systolic function as assessed by fractional area change (FAC) and stroke volume (SV) that were not rescued with normoxia re‐exposure. The aged RV can undergo morphological reverse remodeling following the removal of pathological load; however, RV function does not improve. Further investigation into the mechanisms of reverse remodeling may identify potential drug therapies for maladaptive RV remodeling with aging.