• ABSTRACT
    • Pulmonary arterial hypertension (PAH) is a deadly disease in which vasoconstriction and vascular remodeling both lead to a progressive increase in pulmonary vascular resistance. The response of the right ventricle (RV) to the increased afterload is an important determinant of patient outcome. Little is known about the cellular and molecular mechanisms that underlie the transition from compensated hypertrophy to dilatation and failure that occurs during the course of the disease. Moreover, little is known about the direct effects of current PAH treatments on the heart. Although the increase in afterload is the first trigger for RV adaptation in PAH, neurohormonal signaling, oxidative stress, inflammation, ischemia, and cell death may contribute to the development of RV dilatation and failure. Here we review cellular signaling cascades and gene expression patterns in the heart that follow pressure overload. Most data are derived from research on the left ventricle, but where possible specific information on the RV response to pressure overload is provided. This overview identifies the gaps in our understanding of RV failure and attempts to fill them, when possible. Together with the online supplement, it provides a starting point for new research and aims to encourage the pulmonary hypertension research community to direct some of their attention to the RV, in parallel to their focus on the pulmonary vasculature.