How does the pressure-overloaded right ventricle adapt and why does it fail? Macro-and micro- molecular perspectives

Abstract

The right ventricle (RV) eventually fails in most patients with severe chronic pulmonary hypertension, however, the individual myocardial reserve and ability to cope with the increased afterload, inflammation and metabolic derangements are highly variable. Hypertrophy is required for the RV to successfully adapt to the chronically elevated pressure and shear stress in the lung vessels. RV hypertrophy associated with an appropriate myocardial capillary density and normal function of the capillary endothelial cells are hallmarks of successful adaptation. Neuroendocrine hyperactivity or overdrive may contribute and facilitate the transition from adaptive RV hypertrophy to RV failure. Therapeutic strategies that reduce cellular stress and modify damaging failure components such as inflammation, lipotoxicity and proteotoxicity need to be explored in order to evaluate whether they can preserve RV function and improve outcome, even when the afterload of the RV cannot be significantly reduced.