Fig. 8.

Hypothetical scheme of PH-induced adverse RV remodeling and its reversal by estrogen. In a healthy right ventricle, the ECM is well-ordered and ECM degradation is tightly controlled. Severe PH leads to an increase in RV Akt signaling, and also elevated RV fibrosis, a degradation of general RV ECM proteins and integrins, and a reexpression of ADAMs and fetal gene OPN in the RV. Some OPN leaks into the plasma where it can be used as a biomarker. E2 therapy reduces Akt and ERK signaling and reverses the changes in the ECM, returning the RV to a healthy state.