Table 2.

Current use of various epigenetic modifiers in PAH.

Mechanism	Drug	Targets	Function	Model	Cell type	References
DNMT inhibitor	5-aza-2′-deoxycytidine	DNA methyltransferases 1 and 3B	mPAP↓	FHR rats with PAH	PASMC	Archer et al., 2010
Histone methyltransferase inhibitor	BX-01294	Histone lysine methyltransferase G9a for H3K9me2	P, M↓	PDGF induced proliferation	PASMC	Yang et al., 2012b
Histone demethylase inhibitor	GSK-J4	Histone demethylase JMJD3 for H3K27me3	P↓ Apoptosis↑	IPAH	PAEC	Gambaryan et al., 2013
HDAC inhibitors	Sodium butyrate	HDAC Class I (1,2,3,8)	P, M↓	PDGF induced PH	PASMC	Cantoni et al., 2013
	TSA	HDAC Class I/IIa/IIb/III/IV	RV dysfunction	PAB rats	–	Bogaard et al., 2011
	VPA	HDAC Class I (1,2,3,8)	mPAP↓, RVH↓	Human IPAH, hypoxia rats MCT-induced PAH	PASMC, PH-fibs, “R”-cells Isolated pulmonary arteries	Zhao et al., 2012 Chen et al., 2016
	SAHA	HDAC Class I/II/IV	mPAP↓, RVH↓	Human IPAH, hypoxia rats	PASMC, PH-fibs, “R”-cells	Zhao et al., 2012
	Apicidin	HDAC Class I (1,2,3,8)	RVH↓	Hypoxia mice	PAEC	Yang et al., 2015
	MGCD0130	HDAC Class I (1,2,3)	mPAP↓	Hypoxia rat	PASMC	Cavasin et al., 2012
	MS275	HDAC Class I (1,2,3)	mPAP↓, RVH↓	Hypoxia rat	PASMC	Cavasin et al., 2012
	MC1568	HDAC Class IIa (4,5)	RVSP↓	MCT, SUGEN induced PH, human PAEC	PAEC	Kim et al., 2013, 2015
	Tubastatin A	HDAC6	mPAP↓, RVSP↓	MCT, SUGEN induced PH, human PAH PASMC	PASMC	Boucherat et al., 2017

DNMT, DNA methyltransferase; P, proliferation; M, migration; mPAP, mean pulmonary arterial pressure; PAB, pulmonary artery banding; RVH, right ventricular hypertrophy; RVSP, RV systolic pressure; “R”-cells:morphologically distinct cells potentially of hematopoetic origin with high growth potential (rhomboidal or “R”-cells); MCT, monocrotaline.