Role of histone deacetylase 8 in cardiac hypertrophy in two-kidney two-clip renovascular hypertensive rats

AIM: To investigate the expression and the role of histone deacetylase 8(HDAC8) in cardiac hypertrophy and the effects of valproic acid sodium(VPA,a histone deacetylase inhibitor) on the expression of HDAC8 and cardiac hypertrophy in two-kidney two-clip(2K2C) renovascular hypertensive rats.METHODS: Male SD rats were randomly divided into sham operation group,2K2C group,high dose VPA(400 mg·kg-1·d-1) treatment group,low dose VPA(200 mg·kg-1·d-1) treatment group and candesartan(10 mg·kg-1·d-1) treatment group.Four weeks after surgery,the rats were intraperitoneally injected with VPA for 4 weeks.Sham operation and 2K2C rats were given vehicle for 4 weeks.All animals were sacrificed 8 weeks after surgery.The ratio of left ventricular weight to body weight(LVW/BW) was calculated and pathological changes of the myocardium were observed with HE staining.The mRNA expression of atrial natriuretic factor(ANF) and HDAC8 was examined by RT-PCR.The protein level of HDAC8 was also measured by Western blotting analysis.RESULTS: Compared with the control rats,the mRNA and protein expression of HDAC8 significantly increased in the myocardium in 2K2C rats while the mRNA and protein expression of HDAC8 was significantly decreased by VPA treatment in 2K2C rats.The mass index(as measured by LVW/BW) and cardiomyocyte cross areas were markedly increased and myocardial fibers were disordered in 2K2C rats,but these parameters were markedly reversed after treated with VPA for 4 weeks,indicating that VPA attenuated cardiac hypertrophy.Moreover,VPA also decreased the mRNA expression of ANF.CONCLUSION: HDAC8 may play an important role in cardiac hypertrophy in 2K2C renovascular hypertensive rats.VPA inhibits the expression of HDAC8 and prevents the development of cardiac hypertrophy.