Person: Rhee, Julie S.
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Rhee
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Julie S.
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Rhee, Julie S.
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Publication Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy(Nature Publishing Group, 2012) Patten, Ian S.; Farrell, Caitlin; Tudorache, Igor; Bauersachs, Johann; Hilfiker-Kleiner, Denise; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele; Rhee, Julie S.; Mitchell, John; Mahmood, Feroze-Ud-Den; Hess, Philip; Koulisis, Nicole; Khankin, Eliyahu; Burke, Suzanne; Del Monte, Federica; Karumanchi, Subbian; Arany, Zoltan PierrePeripartum 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.Publication Angiogenic Factors and Renal Disease in Pregnancy(Hindawi Publishing Corporation, 2011) Rhee, Julie S.; Young, Brett; Rana, SaroshBackground: Preeclampsia is difficult to diagnose in patients with underlying renal disease and proteinuria. Prior studies show that there is an angiogenic factor imbalance with elevated levels of antiangiogenic proteins soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) and reduced levels of the proangiogenic protein, placental growth factor (PlGF) in women with preeclampsia. These angiogenic biomarkers may be useful in distinguishing preeclampsia from other conditions of pregnancy, which may present with overlapping clinical characteristics. Cases: Case 1: A multiparous woman at 18 weeks gestation with nephrotic syndrome presented with hypertensive emergency and worsening renal insufficiency. She underwent induction of labor for severe preeclampsia. Her sFlt1 and sEng levels were at the 97 percentile while her PlGF level was undetectable (less than the 1st percentile). Case 2: A nulliparous woman with lupus nephritis at 22 weeks gestation presented with fetal demise and heart failure. Three weeks previously, the patient had developed thrombocytopenia and hypertensive urgency. She underwent dilation and evacuation. Her angiogenic profile was consistent with severe preeclampsia. Conclusion: Angiogenic factors may provide evidence to support a diagnosis of preeclampsia in patients with preexisting renal disease and proteinuria, conditions in which the classical definition of hypertension and proteinuria cannot be used.