Chinese researchers discovered that inhibiting histone deacetylase 1 (HDAC1) could be beneficial in the management of patients with pulmonary arterial hypertension (PAH), according to a study published in Respiratory Research.
In studies involving model rats, HDAC1 has been found to be upregulated in PAH. It is known to inhibit miR-34a expression, which is significant because the downregulation of miR-34a plays an important role in PAH pathogenesis.
When HDAC1 is inhibited, the reversal of monocrotaline (MCT) and hypoxia-induced pulmonary arterial remodeling can be observed. It has been hypothesized that HDAC1 is heavily involved in the pathological remodeling of the extracellular matrix (ECM) through a variety of molecular mechanisms. Researchers thus set out to investigate how HDAC1 affects ECM remodeling in rat models with MCT-induced PAH.
Read more about PAH epidemiology
They injected rat models with MCT intraperitoneally to induce PAH. They inhibited HDAC1 by using the HDAC1 inhibitor MS-275. Researchers also caused the overexpression of miR-34a by injecting miR-34a agomiR at the tail end of the rats.
In rats with MCT-induced PAH, HDAC1 was significantly increased and miR-34a was downregulated. This is consistent with reports from previous literature. What is more interesting are the results of injecting the rat models with MS-275 and miR-34a agomiR:
- HDAC1 was reduced, thus restoring miR-34a expression.
- Pulmonary arterial remodeling was suppressed.
- Excessive ECM accumulation was inhibited.
- Right ventricular systolic pressure was reduced.
- Right ventricular hypertrophy index was reduced.
This shows that the inhibition of HDAC1 increases miR-34a expression, which in turn leads to the whole host of therapeutic benefits for PAH patients mentioned above.
The authors concluded, “The present study demonstrated that inhibition of HDAC1 effectively ameliorates excessive ECM accumulation and pulmonary vascular remodeling in MCT-induced rat PAH, suggesting that inhibiting HDAC1 might be a novel therapeutic strategy in the prevention and treatment of PAH.”
Li F, Wang D, Wang H, Chen L, Sun X, Wan Y. Inhibition of HDAC1 alleviates monocrotaline-induced pulmonary arterial remodeling through up-regulation of miR-34a. Respir Res. 2021;22(1):239. doi:0.1186/s12931-021-01832-7