Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. Given the exacerbated severity of Pulmonary Arterial Hypertension by the interplay of complex genetic and/or epigenetic changes, identification of novel therapeutic avenues via investigation of the epigenetic mechanisms involved in the pathogenesis might be of growing interest.
For example, tissue-specific, methylation-induced SOD2 deficiency increases the proliferation and decreases the apoptosis of PASMC, while also impairing redox signaling. HDAC inhibitors, including SAHA and vorinostat, ameliorate the phenotype of Pulmonary Arterial Hypertension rat models, indicating that increased HDAC activity leads to the pathological condition of PH. Besides, the abnormal expression and dysregulation of miRNAs also contributes to the pathogenesis of this disease.
The current therapies for PAH patients commonly aim to reverse the imbalance of pulmonary vasoactive mediators, such as NO and prostacyclin. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of Pulmonary Arterial Hypertension, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment.