Compositions and methods of inhibiting histone deacetylases
The present invention provides compositions and methods for treating pulmonary hypertension. In one aspect, a method is included for increasing myocyte enhancer factor 2 (MEF2) activity in an endothelial cell comprising exposing the cell to a class IIa histone deacetylase inhibitor. In another aspect, a method is included for treating pulmonary hypertension, such as restoring MEF2 activity, in a subject in need thereof comprising administering to the subject a composition comprising a class IIa histone deacetylase inhibitor. Pharmaceutical compositions for treating pulmonary hypertension in a subject in need thereof and a kit for diagnosing, detecting and/or monitoring pulmonary hypertension are also included.
1. A method for treating pulmonary hypertension in a subject in need thereof comprising administering to the subject a composition comprising tasquinimod or a salt or solvate thereof.
2. The method of claim 1 , wherein the administration increases expression of at least one transcriptional target selected from the group consisting of myocyte enhancer factor 2 (MEF2), kruppel like factor 2 (KLF2), connexin 37 (Cx37), connexin 40 (Cx40), and combinations thereof.
3. The method of claim 1 , wherein the administration decreases expression of fibroblast growth factor 2 (FGF2).
4. The method of claim 1 , wherein the administration decreases proliferation of pulmonary vascular cells.
5. The method of claim 1 , wherein the administration decreases ventricular systolic pressure in the subject.
6. The method of claim 1 , wherein the administration does not induce a caspase pathway activation in pulmonary vascular cells.
7. The method of claim 1 , wherein the administration does not induce myocardial fibrosis.
8. The method of claim 1 , wherein the composition inhibits at least one of HDAC4, HDAC5 and combinations thereof.