Similarly, HDAC inhibitors such as butyrate increase histone H3 acetylation, reduce macrophage accumulation and inflammatory cytokine expression, and prevent or reverse PAH pathological changes (152).Regulation of key signaling pathways is also critical: for example, macrophage-specific deletion of the crucial RNA enzyme Zinc Finger CCCH-Type Containing 12A (ZC3H12A/Regnase-1) aberrantly activates IL-6 and PDGF signaling, leading to spontaneous severe PAH in mice. This evidence concerns the gene IL6 and pulmonary arterial hypertension.