Figure 7.

Summary model of proposed mechanism of AVD progression. TGFβ signaling results in Erk1/2 activation and this in turn stimulates elastase expression ultimately leading to the downstream effects including ECM abnormalities and inflammation. Refametinib or doxycycline treatment, inhibiting p‐Erk1/2 or elastase activation, significantly reverses progression of disease; however, the fact that neither drug returns p‐Erk to its WT levels suggests that Erk1/2 phosphorylation and elastase expression potentiate reciprocally. AVD, Aortic valve disease.