Background
Heart disease could result from a malfunction in the core clock gene BMAL1, according to studies conducted on animals and humans in vitro and in vivo. However, in pathological conditions, the role of BMAL1 was not clear. In the present study, we identified a potential link between BMAL1 and cardiac hypertrophy.
Conclusions
Our results showed that overexpression of BMAL1 effectively resisted cardiac hypertrophy induced by Ang II. Our findings provided a novel potential target for the treatment of cardiac hypertrophy.
Methods
Primary cultured neonatal rat cardiomyocytes were stimulated by Ang II. Cardiomyocytes immunofluorescence analysis was performed to observe the cell size. RT-PCR and Western blot were used to find out the gene and protein expression. Cell apoptosis was measured by TUNEL staining. The Elisa assay was performed which determine the release of cytokines led to the activation of cardiac fibro-blasts in cell-free supernatants. Furthermore, gain- and loss-of-function studies revealed that BMAL1 has an effect on Ang II-induced cardiac hypertrophy.
Results
We found that Ang II-induced cardiac hypertrophy as a result BMAL1 expression was reduced. However, overexpression of BMAL1 could prevent Ang II-induced hypertrophy. Additionally, although BMAL1 overexpression in hypertrophic cardiomyocytes could not prevent hypertrophy, it did reduce the apoptosis of hypertrophic cardiomyocytes after Ang II had induced it. In addition, BMAL1 knockdown did not aggravate Ang II-induced hypertrophy but accelerated its development. Finally, BMAL1 overexpression significantly resisted the effects of Ang II on oxidative stress, autophagy and, cardiac fibrosis in cardiomyocytes. Conclusions: Our results showed that overexpression of BMAL1 effectively resisted cardiac hypertrophy induced by Ang II. Our findings provided a novel potential target for the treatment of cardiac hypertrophy.