Figure 2

Epigenetics and pulmonary hypertension. Methylation of CpG islands in the promoter region of genes can lead to either hypo- or hyperacetylated promoters. This, in turn, can lead to increased or decreased gene transcription. While the pathways are not clearly defined, it is expected that an increase in oncogenes and/or a decrease in tumor suppressor genes can promote the abnormal cell proliferation of PASMCs. RNA interference is a well-described mechanism where miRNAs target specific mRNA and lead to degradation, preventing translation into mature protein. Lastly, histone modifications (either acetylated or methylated lysines and arginines) can promote or prevent transcription factor-mediated gene transcription and lead to increased cell proliferation or apoptosis resistance. These epigenetic mechanisms provide an alternative route for PH development besides mutations associated with the DNA sequence itself. ↑, Increase or upregulation; ↓, decrease or downregulation.