Effects And Mechanisms Of BRCC36 In Pressure Overload-induced Cardiac Fibrosis And Remodeling In Mice

ObjectiveRecent studies have shown that BRCC36 plays an important role in some cardiovascular diseases, it is not understood how it protect heart against hypertrophy and fibrosis. In this study, we aim to investigate the effects of BRCC36 on the chronic overload-induced cardiac hypertrophy and fibrosis in mice.Methods1) constricting transverse aorta (TAC) was used to establish the model of pressure-overload cardiac hypertrophy and fibrosis in the transgenic mice. The experiments were divided into four groups, namely, Wild-type sham group, Wild-type TAC group, transgenic mice sham group, transgenic mice TAC group.2)Eight weeks after TAC, we examined the heart weight index(HWI, heart weight/body weight), left ventricular mass index(LVMI, left ventricular mass/heart weight), expression of special genes and protein associated with cardiac hypertrophy and fibrosis.Results1)Compared with the sham group, HWI and LVWI in TAC group in wild type mice were increased(P<0.05), Meanwhile, HWI and LVWI were significantly increased in Wild-type TAC group as compared with the transgenic mice TAC group.2)Eight week after TAC, Sinus red-stained collagen in cardiac interstitium, especially around the blood vessels, was increased in TAC group, Meanwhile, a significant increase in Wild-type TAC group as compared with transgenic mice TAC group was observed.3)Real-time PCR analysis revealed the connective tissue growth factor(CTGF) and Periostin were significantly decreased in transgenic mice TAC group as compared with Wild-type TAC group.4) Western blot analysis revealed phosphorylated smad3 and y-H2AX expression were significantly decreased in transgenic mice TAC group as compared with Wild-type TAC group (P<0.05), while Rad51 expression was increased.ConclusionOur results have demonstrated that BRCC36 can improve cadiac function and reduce the levels of CTGF and Periostin in transgenic mice harboring gene BRCC36, which has a protective effect though inhibiting the phosphorylation of Smad3, increasing DNA damage repair and reducing the accumulation of DNA damage.