Do antiphospholipid antibodies contribute to increased maternal blood pressure in a rat model of hypertension in preeclampsia?

Abstract

Problem: Preeclampsia is characterised by de novo hypertension and proteinuria during pregnancy pre-ceded by endothelial cell activation. Preeclampsia is triggered by a placental factor(s), one of which maybe necrotic trophoblast debris that is shed from the placenta into the maternal blood. Clearance of necrotic trophoblast debris results in endothelial cell activation in vitro. There are also maternal risk factors for preeclampsia, the strongest of which is anti-phospholipid antibodies (aPL). This work questioned whether necrotic trophoblast debris increased maternal blood pressure in rats and whether aPL exacerbated this effect. Methods of study: Virgin female Wistar rats were surgically implanted with a radio-telemetry blood pressure device and a chronic indwelling vascular port. After surgical recovery, the rats were time mated. Pregnant Wistar rats were injected with necrotic Jeg-3 cells (trophoblast-derived cell line)(n = 5) or vehicle (n = 5) from day 6 to 21 post-coitum (p.c.) at a dose of 5 9 106 cells/Kg body weight. In a separate study, pregnant Wistar rats were injected with an antiphospholipid antibody (n = 5), or an isotype matched control antibody (n = 5), in conjunction with necrotic Jeg-3 cells (trophoblast-derived cell line). Two further groups of pregnant rats received only injections of antiphospholipid antibodies (n = 9) or an isotype matched control antibody (n = 5). Necrotic Jeg-3 cells were given from days 6 to 21 post-coitum (p.c.) at a dose of5 9 106 cells/kg bodyweight and both antibodie swere administered at a dose of 3.5 mg/kg body-weight on days 13 and 18 p.c. Arterial blood pressure was monitored using radio-telemetry and heartrate was calculated from the blood pressure wave. Results: Normalised mean arterial blood pressure of rats receiving injections of necrotic Jeg-3 cells was higher than control rats during the third week of gestation (P = 0.002). However, preliminary results from rats injected with antiphospholipid antibodies suggest that the administration of antiphospholipid antibodies in rats receiving necrotic trophoblasts does not seem to exacerbate this effect. Conclusion: Necrotic trophoblast debris increased maternal blood pressure in rats supporting the hypothesis that necrotic trophoblast debris may be one trigger for preeclampsia. While it appears aPL may not exacerbate this increase in blood pressure, further experiments are required for clarification.