In response to high extracellular Pi levels, it has been shown that an increase in Pi influx induces phosphorylation and activation of the DNA methyltransferase (DNMT1) with subsequent association with the RAS protein activator-like 1 (RASAL1) promoter by histone deacetylase 2 (HDAC2), resulting in RASAL1 promoter cytosine phosphate-guanine (CpG) island hypermethylation which has been implicated in pathological endothelial–mesenchymal transition (EndoMT) in cardiac pathologies such as calcific aortic valve disease and cardiac fibrosis [99,100]. Here, HDAC2 is linked to aortic valve calcification.