A microRNA links prolactin to peripartum cardiomyopathy

Abstract

For decades, peripartum cardiomyopathy has remained an enigma. Despite extensive research, our understanding of how a previously healthy woman can develop lethal heart failure in the context of pregnancy remains vague. Recent work suggests that inadequacy of the cardiac microvasculature may be the primary abnormality and has implicated an antiangiogenic fragment of the nursing hormone prolactin as playing an important role. In this issue of the JCI, Halkein et al. explore signaling downstream of this prolactin fragment and demonstrate that miR-146a is a critical mediator of the antiangiogenic effects in endothelial cells. In addition, the study uncovers unexpected exosomal transfer of this microRNA to cardiomyocytes that may affect myocardial metabolism.

Circulating exosomal miRNAs in cardiovascular disease pathogenesis: New emerging hopes

“…The transported endothelial miR‐146a to their cardiomyocyte recipient cells decreased metabolic pathways via downregulation of Erbb4 , Notch1 , Irak1 , resulting in heart failure. They also revealed that miR‐146a levels were significantly higher in PPCM patients compared with healthy postpartum controls ( p < .001), suggesting the diagnostic role of this microRNA in cardiovascular medicine (Halkein et al, ; Y. Yang, Rodriguez, & Kitsis, ). On the other hand, Ibrahim et al showed that CDCs using exosomes as their mediators have a role in cardiac regeneration and protection.…”

Peripartum cardiomyopathy

“…Subsequent research by the same group showed that 16 kDa prolactin exerts cardiotoxic effects through upregulation of microRNA-146a (miR-146a) 5657. The 16 kDa fragment causes endothelial cells to release exosomes containing miR-146a and other microRNAs.…”

Genetic Polymorphism in Peripartum Cardiomyopathy

“…Towards the end of pregnancy, the placenta systemically secretes soluble FMS-like tyrosine kinase receptor1 (sFLT-1). High sFLT-1 levels can cause cardiomyopathy (23).…”