PERK signaling for PPCM original dataset

Published: 8 March 2021| Version 3 | DOI: 10.17632/tv3kf72yzd.3
Takashi Shimizu


Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure in the peripartum period. Multiple signaling pathways, such as Stat3 and Akt signaling, and various hormones, such as prolactin (PRL) are involved with the pathogenesis. Interactions among them remain unraveled. Therefore, this study aimed to evaluate the contribution of PERK for them. In vivo, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of UPR or JAK/Stat signaling, and upregulation of necroptosis were observed in the hearts of the CM-KO mice. Furthermore, we treated the CM-KO mice with bromocriptine (BCR), reducing the production of PRL. BCR improved postpartum cardiac dysfunction in CM-KO mice, suppressing necroptosis. These results showed that peripartum PERK deletion modulated these interactions.