Patten, Ian S.Farrell, CaitlinTudorache, IgorBauersachs, JohannHilfiker-Kleiner, DeniseRana, SaroshShahul, SajidRowe, Glenn CJang, CholsoonLiu, LauraHacker, MicheleRhee, Julie S.Mitchell, JohnMahmood, Feroze-Ud-DenHess, PhilipKoulisis, NicoleKhankin, EliyahuBurke, SuzanneDel Monte, FedericaKarumanchi, SubbianArany, Zoltan Pierre2013-04-222012Patten, Ian S., Sarosh Rana, Sajid Saleem Shahul, Glenn C. Rowe, Cholsoon Jang, Laura Liu, Michele Renee Hacker, et al. 2012. Cardiac angiogenic imbalance leads to peripartum cardiomyopathy. Nature 485(7398): 333-338.0028-08361476-4687http://nrs.harvard.edu/urn-3:HUL.InstRepos:10579232Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-\(1\alpha\), a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-\(1\alpha\). Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.en-UScell biologymedical researchphysiologymolecular biologyJournal Article2013-04-2210.1038/nature11040