Effect of suberoylanilide hydroxamic acid on diastolic dysfunction in restrictive cardiomyopathy mice

Objective To explore whether suberoylanilide hydroxamic acid (SAHA, br. Vorinostat, a kind of histone deacetylase inhibitor) can improve the diastolic function of restrictive cardiomyopathy (RCM) mice by up-regulating the expression of wild type cardiac troponin I (WT-cTnI). Methods Sixteen male cTnI R193H mice were employed and divided into SAHA group (n=6), dimethyl sulfoxide (DMSO) group (n=5) and control groups (n=5). Mice were subcutaneously injected with 50mg/kg SAHA in SAHA group, with 1ml/kg DMSO in DMSO group and with 1ml/kg normal saline in control group, respectively. The total treatment duration lasted for 56 days. Western blotting was performed to determine the levels of acetylated histone H3 (acH3) and the expression of cTnI. The transcription levels of Tnni3 were detected with RT-qPCR. The levels of acH3 in Tnni3 promoter key area were detected with chromatin immunoprecipitation (ChIP). The data of diastolic function measurements were collected using high frequency echocardiography. Results Compared to control group, the acH3 levels in nucleus and in Tnni3 promoter key area increased significantly in SAHA group (P0.05), but the specific acH3 level in Tnni3 promoter key area increased significantly in SAHA group compared to that in DMSO group (P