INTRODUCTION: Pre-eclampsia (PE) is a severe complication of pregnancy, characterised by maternal hypertension, associated with constriction of the vasculature - an important target for PE treatment. Currently, the antiplatelet drug aspirin is prescribed to prevent PE in women at high risk but is only effective in approximately 10% of cases. New generation antiplatelet drugs (clopidogrel, prasugrel and ticagrelor) are used in clinical cardiovascular disease. More recently we have demonstrated they reduce pathophysiological aspects of PE in both the mouse and human models, revealing their potential to prevent PE and outperform aspirin.
OBJECTIVE: Determine whether new generation antiplatelet treatment could mitigate vascular constriction in systemic maternal vessels (mouse and human). Importantly, we assessed vascular function in direct comparison with aspirin.
METHODS: Mesenteric arteries were dissected from pregnant CBA/C57BL6 (F1) mice on D17.5 gestation (n=4-7). Arteries were dissected from human omental fat biopsies obtained from women at Caesarean Section (n=5). Vessels were mounted onto the Wire Myograph (DMT 620M), normalised and >80% intact endothelium was confirmed. Each vessel was treated with 100uM aspirin, 100uM clopidogrel, 100uM prasugrel, 12.5uM ticagrelor or vehicle control for 30 minutes. Increasing doses of constricting agents, U46619 (human; 10-10M – 10-5.5M) or phenylephrine (mice; 10-9M – 10-5M) were added and constriction assessed.
RESULTS: Mesenteric arteries pre-treated with clopidogrel, prasugrel and ticagrelor demonstrated significantly reduced vascular constriction compared to control, while aspirin did not significantly alter constriction. Likewise, human omental arteries pre-treated with ticagrelor and prasugrel demonstrated reduced vascular constriction to U46619, whereas aspirin and clopidogrel had no significant effect.
CONCLUSION: In contrast to aspirin, new generation antiplatelets demonstrate a novel role in reducing vascular constriction, a pivotal characteristic of PE. These data further demonstrate the distinct multifaceted actions of these agents and their potential to prevent PE, thus translation to clinical trials should be considered.