Implication of the EZH2 methyltransferase and its upstream regulator H19 in pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a progressive condition characterized by the chronic elevation of pulmonary artery (PA) pressure leading to failure of the heart. In spite of recent advances in approved therapies, PAH remains a serious disease with significant mortality. In contrast to the earlier belief that contraction of pulmonary vessels played a key role in PAH, it is now established that excessive proliferation of the cells within the pulmonary artery wall is a pivotal component of pulmonary vascular obliteration, a currently irreversible feature of PAH for which available pharmacotherapies have no/limited efficacy. In recent years, it has become increasingly appreciated that, in addition to rare mutations in genes, changes in their expression in the absence of changes in their structure (i.e. epigenetics) largely contributes to this phenomenon in PAH. Changes in gene expression influence numerous functions of the cells.
This proposal addresses a very novel and promising therapeutic avenue to treat PAH by studying the role of EZH2 in the progressive vascular remodeling seen in PAH.