Poster Session 1
Miriam Hankins, MD (she/her/hers)
Maternal Fetal Medicine Fellow
University of Mississippi Medical Center
Jackson, MS, United States
Nathan Campbell, PhD
Postdoc Research Fellow
University of Mississippi Medical Center
Jackson, Mississippi, United States
Murphy Lemon
University of Mississippi Medical Center
Jackson, Mississippi, United States
E. Hawthorne Cleveland
University of Mississippi Medical Center
Jackson, Mississippi, United States
Emma Grace Joyner
University of Mississippi Medical Center
Jackson, Mississippi, United States
Ella Goolsby
University of Mississippi Medical Center
Jackson, Mississippi, United States
Baoying Zheng, MS
University of Mississippi Medical Center
Jackson, Mississippi, United States
Alexandra Demesa, BS, MS
University of Mississippi Medical Center
Jackson, Mississippi, United States
Evangeline Deer, PhD (she/her/hers)
Instructor
University of Mississippi Medical Center
Jackson, Mississippi, United States
Rachael Morris, MD
Associate Professor
University of Mississippi Medical Center
Jackson, Mississippi, United States
Babbette LaMarca, PhD
Professor and Chair
University of Mississippi Medical Center
Jackson, Mississippi, United States
Pre-eclampsia (PE), new onset hypertension in pregnancy is associated with immune activation, agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA), endothelial dysfunction and increased vasoconstrictor endothelin. The AT1-AA stimulates ET-1 and is produced 7 years postpartum. Prolonged production of AT1-AA indicates a memory immune response, specifically mature memory B cells, in the pathophysiology of PE. The objective of this study was to determine if these B cells cause hypertension and endothelial dysfunction via production of AT1-AA.
Study Design: Three hundred thousand placental CD20+ B Cells from normal pregnant (NP) or PE patients were isolated and injected i.p. into nude athymic rats on gestational day (GD) 12. Mini-osmotic pumps containing the AT1-AA inhibitor peptide, ‘n7AAc’, were inserted on GD14. On GD18, carotid catheters were implanted and mean arterial pressure (MAP) was measured on GD19. Renal Preproendothelin (PPET) was quantified using Real Time-PCR. AT1-AA was quantified using a cardiomyocyte bioassay. A one-way ANOVA was used for statistical analysis.
Results:
Participants had similar age, BMI, and gestational age (36±1 (PE) vs 39±0 (control) weeks) at delivery. PE participants had higher mean arterial pressure (MAP) at delivery than controls (p< 0.05).
MAP was 104±4 mmHg (n=8) in the recipient rats of NP CD20+ B cells which increased to 123±2 mmHg (n=8, p < 0.01) in the recipients of PE B cells. This increase in MAP was lower with ‘n7AAC’, 114±4 mmHg (n=3, p=0.070), an AT1-AA inhibitor peptide. Renal PPET expression increased by 2.60±0.61 fold (ΔΔct) in PE B cell recipients (p< 0.05) compared to NP B cell recipients and tended to be lower in ‘n7AAc’ treated rats 0.85±0.35 Fold (p=0.19). AT1-AA activity was elevated in the PE B cell recipients (14±2 ΔBPM) compared to NP B cell (1±1 ΔBPM, p< 0.01) and ‘n7AAc’ treated PE B cell recipients (2±3 ΔBPM, p< 0.05).
Conclusion:
CD20+ B cells from PE women contribute to hypertension and AT1-AA medicated endothelial activation during pregnancy, thereby supporting an important role for B cells in the pathophysiology of PE.
