However, several of these mechanisms may merge into a common major pathway, which includes unbalanced oxidative stress and the cleavage of the nursing hormone prolactin (PRL) into an angiostatic, pro-apoptotic, and pro-inflammatory 16 kDa-PRL fragment, resulting in subsequent vascular damage and heart failure.
We recently demonstrated beneficial effects associated with the prolactin release inhibitor bromocriptine at different doses when added to standard heart failure therapy in PPCM.
The lactation-blocking drug bromocriptine prevents prolactin release and promotes healing of PPCM in combination with pharmacological heart failure therapy; it appears to prevent recurrence in subsequent pregnancies.
In mice with PPCM due to a cardiomyocyte-specific knockout of STAT3 (CKO) neither low nor high dose of recombinant Relaxin-2 (serelaxin, sRlx-LD: 30 µg/kg/day; sRlx-HD: 300 µg/kg/day) affected cardiac fibrosis, inflammation and heart failure but sRlx-HD increased capillary/cardiomyocyte ratio. sRlx-HD significantly increased heart/body weight ratio and cardiomyocyte cross-sectional area in postpartum CKO and wild-type mice without changing the foetal gene expression program (ANP or β-MHC). sRlx-HD augmented plasma Prolactin levels in both genotypes, which induced cardiac activation of STAT5.
Prolactin represents a stimulatory link between the neuroendocrine and immune systems, but its involvement in the neurohumoral adaptations to heart failure (HF) has not been explored.