Tauroursodeoxycholic acid rescues stress-induced reduction of proliferation and increased apoptosis in cardiomyocytes.

Tauroursodeoxycholic acid (TUDCA) has been known for its roles in enhancing cell proliferation and reducing apoptosis in cardiomyocytes proposing it as a valuable treatment approach putatively especially in the context of stress-induced cardiovascular dysfunction. In this study, we (1) investigated the detrimental effects of stress on both cell proliferation and apoptosis in cardiomyocytes, and subsequently (2) assess the role of TUDCA in preventing these detrimental changes. AC16 cardiomyocytes were treated with cortisol 100 μM alone or in combination with bile acids TUDCA (10-100 μM) for 24 hours. Immunocytochemistry was then performed to identify changes in proliferation (with the marker Ki67) and cell apoptosis (with the marker caspase 3 (CC3)). Results show that cortisol significantly decreased the number of Ki67+ cells (cortisol vs control: -12%, p<0.001) and increased the number of CC3+ cells (cortisol vs control: +9%, p<0.01). Interestingly, treatment with TUDCA (both 10 and 100 μM) fully prevented cortisol-induced reduction in Ki67+ cells (cortisol + 10 or 100 μM TUDCA vs cortisol: +14%, p<0.001, for both), while treatment with TUDCA (only 10 μM) fully prevented cortisol-induced increase in CC3+ cells (cortisol + 10 μM TUDCA vs cortisol: -8%, p<0.01). Overall, our results suggest that cortisol can reduce proliferation and increase apoptosis in cardiomyocytes, and that TUDCA can prevent these detrimental changes. This work is supported by the European Union's Horizon 2020 research and innovation programme (grant n° 848158). [ABSTRACT FROM AUTHOR]