Exosome Cargo From Preeclamptic Patients Mediates Endothelial Dysfunction, Subsequent Cardiovascular Remodeling, and the Preeclamptic Phenotype
Although extensively studied, the cause of preeclampsia remains uncertain other than it is thought that the placenta plays a critical role in the development of preeclampsia. Recent data revealed that exosomes released from the placenta could cause preeclampsia by transporting specific cargo responsible for the pathophysiological changes associated with the systemic disease. By isolating these exosomes from maternal blood and placental tissue in patients diagnosed with preeclampsia and studying their biochemical, cellular and molecular mechanism in an animal model, the investigators hope to elucidate the critical role that exosomal cargo plays in the development of preeclampsia and cardiovascular remodeling. This will be accomplished by obtaining patient samples from volunteers delivering at the Women and Infants Center and taking the samples to the lab for quantification, characterization, and identification of key functional roles through in/ex vivo, in vitro, and profiling studies. The investigators believe this work will be valuable as hope exists to define the functional role exosomes play in the development of preeclampsia that leads to cardiovascular remodeling. Data from this study will shed more light on the functional role of exosomal cargo in normal and pathological pregnancies and point towards novel therapeutic intervention strategies for preeclampsia associated with cardiovascular disease.
• Preeclampsia patients: Age ≥ 18 years; Diagnosis of preeclampsia with severe features:
‣ BP ≥160/110 after 20 weeks gestation AND ≥300 mg/day proteinuria or protein/creatinine ratio of 0.3 mg/dL; OR
⁃ BP ≥160/110 after 20 weeks gestation with any of the following co-conditions: platelet count less than 100,000 X 109/L, AST/ALT enzymes elevated to twice the upper limit of normal, serum creatinine ≥1.1 mg/dL or a doubling of the creatinine from baseline, pulmonary edema, new-onset headache, and/or visual disturbances.
• Control patients: Age ≥ 18 years; no diagnosis of preeclampsia or any pregnancy-induced hypertension disorder.
• Pre-clampsia patients will be defined as =140 mmHg systolic or =90mmHg diastolic BP with at least at least 2 occasions 4 hours apart after 20 weeks of gestation in previously normotensive women with at least one of the following symptoms: =300 mg/day proteinuria, protein/creatinine ratio of 0.3 mg/dL, platelet count \< 100,000 X 109/L, elevated liver enzymes, serum creatinine =1.1 mg/dL, pulmonary edema, or new-onset headache or visual disturbances.
‣ \>22w 0d gestational age -33w 6d GA (n=16)
⁃ \>= 34 wGA (n=16)
• Pre-eclampsia with severe features will be defined as blood pressure =160 mmHg systolic or =110 mmHg diastolic BP at least 2 occasions 4 hours apart after 20 weeks of gestation with any of the additional diagnostic criteria listed above.
‣ \>22w 0d gestational age -33w 6d GA (n=16)
⁃ \>= 34 wGA (n=16)
• Healthy gestational age matched controls:
‣ \>22w 0d gestational age -33w 6d GA (n=32)
⁃ \>= 34 wGA (n=32)