Mice lacking the transcription factor STAT3 or the transcriptional coactivator PGC1α in cardiomyocytes provide models of PPCM. While absence of STAT3 or PGC1α in cardiomyocytes may not be inciting events in human PPCM, these mouse models have helped to reveal the underlying molecular pathogenesis. Absence of these proteins results in decreased expression of the ROS scavenger MnSOD in these cells. Decreased MnSOD levels result in ROS accumulation, increasing and activating Cathepsin D, which is secreted from cardiomyocytes into the interstitial space. Cathepsin D cleaves PRL to generate an antiangiogenic 16-kDa fragment, 16K PRL. 16K PRL stimulates endothelial cells through an unknown mechanism to activate NF-κB, which increases levels of miR-146a. miR-146a decreases levels of NRAS, inhibiting angiogenesis. In addition, miR-146a transits to cardiomyocytes in exosomes to decrease levels of ERBB4, resulting in slowed cardiac metabolism. VEGF levels are decreased by the absence of PGC1α in cardiomyocytes (not shown), and VEGF is antagonized by the secretion of sFLT1 from the placenta, both mechanisms inhibiting angiogenesis. Triggering events in human PPCM include generation of 16K PRL and increases in miR-146a and sFLT1.