Peripartum cardiomyopathy (PPCM) is a deterioration in cardiac function that occurs in pregnant women during the last month or in the months following their pregnancy. This disorder can occur in women with no prior history of heart disease and the causes are not well understood. Julie Halkein and colleagues identified a molecule, miR-146a, that can serve as a biomarker for peripartum cardiomyopathy. Halkein and colleagues found that expression of miR-146a was induced by the nursing hormone prolactin and that miR-146a was elevated in the serum of pregnant women who later developed PPCM. Prolactin acts directly on the endothelial cells that line blood vessels, inhibiting migration and inducing cell death. The endothelial cells release exosomes that contain miR-146a into the blood and surrounding environment. These miR-146a-loaded exosomes are absorbed by both endothelial cells and cardiomyocytes, which form the heart muscle. The accompanying image is an electron micrograph of neonatal rat cardiomyocytes absorbing miR-146a exosomes. miR-146a blocked the formation of new blood vessels (angiogenesis) and impaired the metabolism and function of cardiomyocytes. These findings identify key pathological mechanisms and indicate that miR-146a could serve as a biomarker for PPCM.
Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of
Julie Halkein, Sebastien P. Tabruyn, Melanie Ricke-Hoch, Arash Haghikia, Ngoc-Quynh-Nhu Nguyen, Michaela Scherr, Karolien Castermans, Ludovic Malvaux, Vincent Lambert, Marc Thiry, Karen Sliwa, Agnes Noel, Joseph A. Martial, Denise Hilfiker-Kleiner, Ingrid Struman