© 2015 Tao et al. Abstract Background: Lately, there is accumulating evidence that the Wnt/Frizzled pathway is reactivated after myocardial infarction, the inhibition of the pathway is beneficial since it reduce of myocardial apoptosis and prevents heart failure. FrzA/Sfrp-1, a secreted frizzled-related protein and antagonist for the wnt/frizzled pathway. We assessed the hypothesis that FrzA protects cardiomyocytes from H < inf > 2 < /inf > O < inf > 2 < /inf > -Induced Oxidative damage through the inhibition of Wnt/Frizzled pathway activity. Methods: We used a recombinant AAV9 vector to deliver FrzA gene into neonatal rat ventricle myocytes and developed an oxidative stress model using H < inf > 2 < /inf > O < inf > 2 < /inf > . The cell vitality was measured by MTT colorimetric assay. Western blot and RT-PCR were used to evaluate the expressions of Dvl-1, β-catenin, c-Myc, Bax and Bcl-2. Flow cytometry analysis of cardiomyocytes apoptosis. Results: We confirmed that Wnt/frizzled pathway is involved in H < inf > 2 < /inf > O < inf > 2 < /inf > -induced apoptosis in cardiomyocytes. Compared with controls, H < inf > 2 < /inf > O < inf > 2 < /inf > induced the upregulation of Dvl-1, β-catenin, and c-Myc. FrzA suppressed the expression of Dvl-1, β-catenin, c-Myc and the activity of the Wnt/frizzled pathway. Furthermore, FrzA over-expression decreased the apoptotic rate, and the Bax/Bcl-2 ratio in cardiomyocytes treated with H < inf > 2 < /inf > O < inf > 2 < /inf > . Conclusions: FrzA, through the inhibition of Wnt/Frizzled pathway activity reduced H < inf > 2 < /inf > O < inf > 2 < /inf > -induced cardiomyocytes apoptosis and could be a potential therapeutic target for prevention of cardiac oxidative damage.
Tao, J., Chen, B. D., Ma, Y. T., Yang, Y. N., Li, X. M., Ma, X., … Chen, Y. (2015). FrzA gene protects cardiomyocytes from H<inf>2</inf>O<inf>2</inf>-induced oxidative stress through restraining the Wnt/Frizzled pathway. Lipids in Health and Disease, 14(1). https://doi.org/10.1186/s12944-015-0088-0