Table 2.
Histone deacetylases in PH: published evidence
| Species | Model/tissues/cells | Summary | Reference |
|---|---|---|---|
| Rat | PAB; RV | Suppression of HDACs (TSA) worsens RV dysfunction after PAB | Bogaard et al.116 |
| Bovine | Hypoxia; adventitial fibroblasts | Alterations in class (I) HDAC1/2/3 expression and activity contribute to a proinflammatory phenotype of PH-fibroblasts and was attenuated by application of HDAC inhibitors (SAHA, apicidin) | Li et al.83 |
| Human/bovine/rat | Increased expression of HDAC1/4/5 in IPAH lung homogenates, HI PH lungs and RV; HDAC inhibition (SAHA, VPA) attenuated the development of HI PH and hyperproliferative phenotype of PH-fibroblasts and R-cells from hypertensive bovine pulmonary arteries | Zhao et al.115 | |
| Human | IPAH; lungs | ||
| Bovine | Adventitial fibroblasts, R-cells | ||
| Rat | Hypoxia; lungs, RV | ||
| Rat | Hypoxia; RV, PASMCs | Selective class I HDAC inhibitors (MGCD0103 and MS-275) suppresses HI PH and RVH in a preclinical model of hypoxia-mediated PH | Cavasin et al.114 |
| Ovine (sheep) | Serum; PASMCs | Inhibition of class I and II HDACs by apicidin and HDACi VIII suppressed serum-induced proliferation and migration of newborn PASMCs | Yang et al.117 |
| Rat | PDGF; PASMCs | Sodium butyrate inhibits PDGF-induced proliferation and migration in PASMCs through Akt inhibition | Cantoni et al.118 |
| Rat | PDGF; PASMCs | Class I HDAC inhibitor (MC1855), but not class II HDAC inhibitor (MC1575), counteracts PDGF-induced proliferation and migration of PAH PASMCs | Galletti et al.119 |
| Bovine | Hypoxia; adventitial fibroblasts | Pan-HDAC inhibitors (SAHA, apicidin) rescued the HI downregulation of antiproliferative miR-124 expression in hypoxic adventitial fibroblasts | Wang et al.120 |
| Rat | MCT, SuHx-PH, PAB | Pan-HDAC inhibitor TSA has no therapeutic or beneficial effects in SuHx-PH | De Raaf et al.121 |
| Human | IPAH PAECs, MCT, SuHx-PH | Increased nuclear accumulation of class IIa HDACs HDAC4 and HDAC5 impaired MEF2 activity in PAH PAECs; pharmacological inhibition of class IIa HDACs using MC1568 rescued the impaired MEF2 transcriptional activity in PAH PAECs and also reduced PAH PAEC proliferation and migration; no evidence of myocardial fibrosis in MCT and SuHx groups upon HDAC inhibition | Kim et al.33 |
Note
HDAC: histone deacetylase; HI: hypoxia-induced; IPAH: idiopathic PAH; MCT: monocrotaline; MEF2: myocyte enhancer factor; PAB: pulmonary artery banding; PAECs: pulmonary artery endothelial cells; PAH: pulmonary arterial hypertension; PASMCs: pulmonary artery smooth muscle cells; PDGF: platelet-derived growth factor; RV: right ventricle/ventricular; RVH: RV hypertrophy; SAHA: suberoylanilide hydroxamic acid; SuHX-PH: hypoxia+SU5416–induced PAH (SU5416 is a vascular endothelial growth factor receptor [VEGFR-2] inhibitor); TSA: trichostatin A; VPA: valproic acid.