Journal Article Epublish
PubMed: 39587642 DOI: 10.1186/s13293-024-00672-6
3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.
Biol Sex Differ 15(1):94
Authors: Clara Liu Chung Ming, Dillan Pienaar, Sahar Ghorbanpour, Hao Chen, Lynne Margaret Roberts, Louise Cole, Kristine C McGrath, Matthew P Padula, Amanda Henry, Carmine Gentile, Lana McClements
Affiliations
- School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW, Australia. Heart Research Institute, Sydney, Australia.
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
- Department of Women's and Children's Health, St. George Hospital, Sydney, NSW, Australia.
- St George and Sutherland Clinical Campus, School of Clinical Medicine, University of New South Wales Medicine and Health, Sydney, NSW, Australia.
- Australian Institute of Microbiology and Infection, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
- Department of Women's and Children's Health, St. George Hospital, Sydney, NSW, Australia. St George and Sutherland Clinical Campus, School of Clinical Medicine, University of New South Wales Medicine and Health, Sydney, NSW, Australia. Discipline of Women's Health, School of Clinical Medicine, University of New South Wales Medicine and Health, Sydney, NSW, Australia.
- School of Biomedical Engineering, Faculty of Engineering and Information Technology, University of Technology Sydney, Sydney, NSW, Australia.
- Heart Research Institute, Sydney, Australia.
- School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Abstract
BACKGROUND
Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with increased cardiovascular disease (CVD) risk, although mechanisms are poorly understood.
METHODS
Human induced pluripotent stem cells (iPSC)-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were cocultured to form cardiac spheroids (CSs) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum [n = 5 per group: normotensive control, gestational hypertension (GH) and preeclampsia (PE)]. Plasma-treated CSs were assessed for cell viability and contractile function and subjected to immunofluorescence staining and imaging. A quantitative proteomic analysis of plasma samples was conducted (controls n = 21; GH n = 5; PE n = 12).
RESULTS
Contraction frequency (CF) was increased in PE-treated CSs (CF: 45.5 ± 3.4 contractions/minute, p < 0.001) and GH-treated CSs (CF: 45.7 ± 4.0 contractions/minute, p < 0.001), compared to controls (CF = 21.8 ± 2.6 contractions/min). Only PE-treated CSs presented significantly increased fractional shortening (FS) % (9.95 ± 1.8%, p < 0.05) compared to controls (3.7 ± 1.1%). GH-treated CSs showed a reduction in cell viability (p < 0.05) and an increase in α-SMA expression (p < 0.05). Proteomics analyses identified twenty differentially abundant proteins, with hemoglobin A2 being the only protein perturbed in both GH and PE versus control plasma (p < 0.05).
CONCLUSIONS
The innovative patient-relevant CS platforms led to the discovery of biomarkers/targets linked to cell death signaling and cardiac remodeling in GH-induced CVD and vascular/endothelial cell dysfunction in PE-induced CVD.
MeSH
Cells, Pregnancy, Cell Survival, Endothelial Cells, Postpartum Period, Plasma