Scientific Reports (Sep 2021)

Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction

  • Takashi Shimizu,
  • Akashi Taguchi,
  • Yoshiki Higashijima,
  • Yasuharu Kanki,
  • Ryo Nakaki,
  • Yoshihiro Urade,
  • Youichiro Wada

DOI
https://doi.org/10.1038/s41598-021-98344-7
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 12

Abstract

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Abstract Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term.