Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Maternal C1q deficiency: Implications for cardiovascular adaptations and pregnancy outcome. (#34)

Evangeline A Lovell 1 , Shanna L Hosking 1 , Holly M Groome 1 , Matthew Chapman 2 , Sven Y Surikow 2 , Laura J Parry 3 , Sarah A Robertson 1 , Alison S Care 1
  1. Robinson Research Institute and School of Biomedicine, University of Adelaide, Adelaide, SA, Australia, University of Adelaide, Adelaide, SA, Australia
  2. Cardiology Unit, Lyell McEwin Hospital, Northern Adelaide Local Health Network, Adelaide, SA, Australia
  3. Robinson Research Institute and School of Biosciences, University of Adelaide, Adelaide, SA, Australia, University of Adelaide, Adelaide, SA, Australia

Cardiovascular complications of pregnancy such as preeclampsia predispose women to later life obesity, metabolic syndrome, and cardiovascular disease. Some women with preeclampsia exhibit low peripheral blood concentrations of complement regulatory protein C1q. C1q may be involved in the events of placental development, but its precise physiological role has not been investigated. We therefore hypothesised that maternal C1q deficiency could impair maternal cardiovascular function and lead to adverse pregnancy outcomes.

To investigate this, female mice with a null mutation in C1qa (C1qa-/- mice) were mated to BALB/c males. Wild-type C57BL/6 females mated to BALB/c males served as controls. Blood pressure was measured before and during pregnancy using tail cuff plethysmography. Uterine artery function was evaluated on day 9.5 post coitum (pc) using ultrasound bio-microscopy, and cardiac function was assessed on day 17.5pc using echocardiography.

There were no differences in mean arterial pressure (MAP) between C1qa-/- and wild-type mice before or during mid-pregnancy. However, in late-pregnancy, MAP decreased in wild-type mice, but not in C1qa-/- mice, indicative of impaired haemodynamic adaptation. In mid-pregnancy, uterine artery dysfunction was evident, with a 16% increase in uterine artery resistance index. Impaired uterine spiral artery remodelling was also observed, with a 41% reduction in artery lumen area, and an 11% reduction in uNK cell abundance (P<0.05). There was evidence of cardiac dysfunction in C1qa-/- dams in late-pregnancy with a 20% increase in cardiac weight, a 29% increase in left ventricular mass, and a 39% increase in cardiac output, compared to wild-type mice (all P<0.05).

These data demonstrate that maternal C1q deficiency has adverse consequences for maternal cardiovascular adaptations to pregnancy. This underscores the significance of C1q as a key immune regulator in cardiac function and vascular adaptations and identifies C1q as a candidate target for interventions to optimise pregnancy success and postpartum cardiovascular health.