Table 3.

Characteristics of HDAC inhibitors and activators in vascular calcification.

HDAC Modulator	Chemical Classification	HDAC Specificity	Effect on VC	Study Model	Cell Type	Mechanism	References
HDAC inhibitor
Apicidin	Cyclic peptide	Class I	Promote	2 mM Pi	RVSMCs	Reduces HDAC1 and increases Runx2	[116]
Trichostatin A	Hydroxamic acid	Class I, II, IV	Promote	3 mM Pi	HASMCs	Reduces HDAC1 and increases Runx2	[184]
Vorinostat	Hydroxamic acid	Class I, II, IV	Promote	1.5 mM Ca2+ and 2 mM Pi	pVICs	Enhances H4 acetylation, Runx2, and OPN	[107]
Tubacin	Hydroxamic acid	HDAC6	Promote	10 mM β-GP, 10 nM DM, 4 μg/mL vitamin D3, and 8 mM CaCl2	hVICs	Activates ER stress and increases Runx2	[132]
Sirtinol	Benzamide	SIRT1, SIRT2	Promote	5 mM β-GP and 2.6 mM CaCl2	HCASMCs	Increase senescence and promotes Runx2 and osteocalcin	[171]
Entinostat	Benzamide	Class I, IV	Inhibit	10 nM DM, 10 mM 10 mM β-GP, and 50 mg/mL AA	pVICs	Reduce Wnt signaling, Runx2, and ALP	[185]
Valproic acid	Short-chain fatty acids	Class I, IIa	Inhibit	3mM Pi	BASMCs	Enhances autophagy and reduces Runx expression	[186]
Sulforaphane	Isothiocyanate	Class III	Inhibit	770 mg β-GP, 11 mg L-AA, and 10 nM DM	RVSMCs	Reduces oxidative stress and Runx2	[187]
HDAC activator
Resveratrol	Stilbenoid	SIRT1, SIRT2	Inhibit	3.2mM Pi or 770 mg β-GP, 11 mg L-AA, and 10 nM DM	HASMCs or RVSMCs	Reduces senescence and Runx2 and increases Nrf2	[133,188]

Pi, inorganic phosphate; β-GP, β-glycerophosphate; DM, dexamethasone; AA, ascorbic acid; RVSMCs, rat vascular smooth muscle cells; HASMCs, human aortic smooth muscle cells; pVICs, porcine aortic valvular interstitial cells; hVICs, human aortic valvular interstitial cells; HCASMCs, human coronary artery smooth muscle cells; BASMCs, bovine aortic smooth muscle cells; and Nrf2, nuclear factor-erythroid related factor 2.