The Placenta in Maternal and Fetal Cardiovascular Health and Disease

• S. Ananth KARUMANCHI, Cedars-Sinai Medical Center (USA)
• Didier STAINIER, Max Planck Institute for Heart and Lung Research (Germany)

The placenta is at the epicenter of maternal and fetal health. It is a large, highly vascular, and highly hormonal organ that both sustains fetal development and simultaneously reprograms maternal physiology. Experimental studies in mice and human clinical and epidemiological data demonstrate that placental dysfunction is tightly linked to substantial cardiovascular disease (CVD), in both mother and child. Despite these findings, placental causes of CVD remain overlooked, understudied and poorly treated. The PlacHeart network’s overarching goal is to understand the molecular and cellular mechanisms by which the placenta affects maternal and fetal cardiovascular function and causes maternal and fetal CVD. Our laboratories have recently developed new tools to genetically and molecularly characterize placental biology in mouse, and we have collected well-phenotyped placental tissue and blood samples from large cohorts of patients with maternal and fetal CVD. Now is therefore an opportune time to tackle the critical question of how placental dysfunction contributes to CVD. We propose using mouse and zebrafish genetic tools, analysis of human tissues and genetics, and ex vivo approaches to identify novel pathogenic pathways by which placental dysfunction leads to maternal CVD and congenital heart defects (CHDs) in the offspring. To accomplish these objectives, we have assembled a synergistic team of investigators with expertise in placental syndromes, maternal heart failure, CHD, mouse and human placental and developmental biology, CVD, and human epidemiology. Our ultimate goal is to identify novel mechanisms and therapies for maternal and fetal CVD linked to placental dysfunction.