Abstract 46: Peripheral Inflammation Prior to rhe Onset of Hypertension and Proteinuria Characterizes the BPH/5 Mouse Model of Preeclampsia

Abstract

Evidence suggests that the immune system plays an important role in the pathogenesis of preeclampsia (PE), a hypertensive disease of pregnancy. Increased levels of circulating pro-inflammatory Th1 polarized T cells have been observed in PE patients. However, because it is not possible to diagnose PE until after its onset at ∼20 weeks of pregnancy, it is not known whether overactivity of the immune system is a cause or an effect of this disease. The BPH/5 mouse strain spontaneously develops the hallmarks of PE, including late-gestational (∼e14-16) hypertension and proteinuria, making it a valuable model system for studying early-pregnancy factors that may play a causal role in PE. Here we utilized flow cytometry to measure inflammatory cells and tested the hypothesis that BPH/5 mice exhibit T cell activation prior to the development of PE. First, similar to humans, there are increased circulating pro-inflammatory T cells at the hypertensive late-gestation stage (e18.5) in BPH/5 mice compared to C57Bl/6 controls (11 ± 0.2 x 10 5 vs 1.5 ± 0.4 x 10 5 CD3 + cells, n=5; p<0.05). Aortas of BPH/5 mice at this time-point also show increased CD3 + T cells compared to C57 (7.2 ± 1.2 x 10 3 vs 1.1 ± 0.4 x 10 3 CD3 + cells, n=5; p<0.05). Next, to investigate if peripheral inflammation is increased before the onset of PE in this model, we measured circulating and aortic pro-inflammatory T cells at e10.5. BPH/5 mice showed a significant increase in both circulating (7.8 ± 0.2 x 10 5 vs 2.2 ± 0.2 x 10 5 CD3 + cells, n=5; p<0.05) and aortic (3.9 ± 0.9 x 10 3 vs 0.8 ± 0.2 x 10 3 CD3 + cells, n=5; p<0.05) T cells compared to controls. These data demonstrate that BPH/5 mice, similar to humans, show peripheral inflammation during PE. However, more importantly, our data show that activation of the immune system occurs prior to the onset of hypertension and proteinuria in this model, suggesting that peripheral inflammation may play a causal role in this devastating disease of pregnancy.