THE ROLE OF MICRORNAS IN PERIPARTUM CARDIOMYOPATHY



Nandini Nair, M.D., Providence Sacred Heart Medical Center, Spokane, WA, USA

Peripartum cardiomyopathy (PPCM) causes considerable morbidity and mortality in young women during their reproductive years. The presentation is usually in the month preceding delivery up to 5 weeks post-partum. This overview will address some of the new developments in the field of molecular medicine using micro RNAs for diagnosis and also as therapeutic targets. In normal pregnancy reactive oxygen species increases ROS production reverting to normal levels in the post-partum period .However the total anti-oxidant capacity also increases during pregnancy and continues to be elevated post-partum. Studies on mice with Stat3 deletion have revealed the link between oxidative stress and prolactin. The increase in reactive oxygen species (ROS) in this murine model was associated with cleavage of the hormone prolactin (PRL) by ROS-activated Cathepsin D. These mice showed increased expression/activity of cathepsin D associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of prolactin. Bromocriptine prevented PPCM in the STAT3 deleted mice. The 16 kDa form of prolactin impaired the cardiac capillary network and function in the myocardium resulting in the cardiac phenotype of PPCM. The micro RNA mir146-a has been implicated in the regulation of the prolactin signaling pathway. The 16K prolactin fragment exerts negative effects in endothelial cells by up regulating miR-146a. Additionally mir-146a levels were increased in patients with PPCM which resolved after treatment with bromocriptine possibly defining the role of prolactin in the pathophysiology of PPCM.