Oral Presentation ESA-SRB-NZSE-CaSR 2026 in conjunction with ENSA

Evaluating Potential Treatments Targeting Angiogenesis in Preeclampsia (144054)

Fatemeh FH Heidari 1 2 , Ahmed Elkashif 3 , Tracy Robson 4 , Helen McCarthy 3 , Kristine McGrath 1 , Lana McClements 1 2
  1. School of Life science, University of Technology Sydney, Sydney, NSW, Australia
  2. Institute for Biomedical Materials and Devices, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia
  3. School of Pharmacy, Queen's University Belfast, Belfast , Northern Ireland, UK
  4. School of Pharmacy and Biomolecular Sciences, University of Medicine and Health Sciences, Dublin, Ireland, UK

Aim: This study established a novel in vivo model of preeclampsia by inducing angiogenic imbalance (high sFlt-1/low FKBPL) and evaluated the impact of potential therapies for preeclampsia prevention and treatment a.

 

Method: Wild-type (WT) and fkbpl+/-C57BL/6N mice were administered sFlt-1 (5μg) using a non-viral gene delivery system, RALA, as nanoparticles, intravenously on embryonic days E8 and 12 and randomly allocated to i) control (n=10), ii) exercise (n=5), iii) metformin (n=7), iv) FKBPL-based peptide, AD-01(n=8), or v) RALA-hFlt-1(n=8) groups. Echocardiography and placenta/embryo weight were determined, and placentas were harvested on day E18.  

 

Results: RALA-sFlt-1 (<100 nM, 40–60 mV) nanoparticles reduced embryo weight in WT (female/male: p<0.0001) and fkbpl⁺/⁻ mice (female: p<0.05; male: p<0.01), compared to vehicle control. Exercise improved embryo weight only in sFlt-1 fkbpl⁺/⁻ mice (female/male: p<0.0001) in conjunction with higher placental efficiency (p<0.0001) and reduced placental sFlt-1 concentration (male: p<0.001; female: p<0.05). AD-01 improved embryo weight in sFlt-1 WT (female: p<0.01; male: p<0.05). RALA-hFlt-1 improved embryo weight in sFlt-1 WT mice (female: p<0.0001; male: p<0.01), together with placental efficiency in female mice only (p<0.0001). However, in sFlt-1 fkbpl⁺/⁻ mice, RALA-hFlt-1 improved embryo weight (female: p<0.001; male: p<0.01), but no change was observed in placental efficiency. Placental sFlt-1 concentration was significantly increased in female fkbpl⁺/⁻ (p<0.05) compared to WT. Cardiac output was reduced in sFlt-1 group in WT mice only (p<0.05). In fkbpl⁺/⁻ mice, exercise increased cardiac output (p<0.05).

 

Conclusion: Our preeclampsia model of angiogenic imbalance impairs maternal cardiovascular and fetal outcomes; exercise, AD-01, and RALA-hFlt-1 show variable, fkbpl-dependent therapeutic effects.

  1. References: a McNally R, Alqudah A, McErlean EM, Rennie C, Morshed N, Short A, McGrath K, Shimoni O, Robson T, McCarthy HO, McClements L. Non-viral gene delivery utilizing RALA modulates sFlt-1 secretion, important for preeclampsia. Nanomedicine. 2021 Sep 1;16(22):1999-2012.