3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.

Chung Ming, CL; Pienaar, D; Ghorbanpour, S; Chen, H; Roberts, LM; Cole, L; McGrath, KC; Padula, MP; Henry, A; Gentile, C; McClements, L

3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.

Chung Ming, CL Pienaar, D Ghorbanpour, S Chen, H Roberts, LM Cole, L

McGrath, KC Padula, MP Henry, A Gentile, C

McClements, L

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: Biol Sex Differ, 2024, 15, (1), pp. 94
Issue Date:: 2024-11-25

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Field	Value	Language
dc.contributor.author	Chung Ming, CL
dc.contributor.author	Pienaar, D
dc.contributor.author	Ghorbanpour, S
dc.contributor.author	Chen, H
dc.contributor.author	Roberts, LM
dc.contributor.author	Cole, L https://orcid.org/0000-0001-9206-9272
dc.contributor.author	McGrath, KC
dc.contributor.author	Padula, MP
dc.contributor.author	Henry, A
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2024-12-15T23:50:41Z
dc.date.available	2024-11-07
dc.date.available	2024-12-15T23:50:41Z
dc.date.issued	2024-11-25
dc.identifier.citation	Biol Sex Differ, 2024, 15, (1), pp. 94
dc.identifier.issn	2042-6410
dc.identifier.issn	2042-6410
dc.identifier.uri	http://hdl.handle.net/10453/182538
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation	National Heart Foundation of Australia106628
dc.relation.ispartof	Biol Sex Differ
dc.relation.isbasedon	10.1186/s13293-024-00672-6
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	3105 Genetics
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Hypertension, Pregnancy-Induced
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Postpartum Period
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Adult
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Humans
dc.subject.mesh	Hypertension, Pregnancy-Induced
dc.subject.mesh	Postpartum Period
dc.subject.mesh	Pregnancy
dc.subject.mesh	Adult
dc.subject.mesh	Female
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Pregnancy
dc.subject.mesh	Hypertension, Pregnancy-Induced
dc.subject.mesh	Myocytes, Cardiac
dc.subject.mesh	Postpartum Period
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Induced Pluripotent Stem Cells
dc.subject.mesh	Fibroblasts
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Adult
dc.title	3D in vitro modelling of post-partum cardiovascular health reveals unique characteristics and signatures following hypertensive disorders in pregnancy.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Health Technologies (CHT)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Australian Institute for Microbiology & Infection (AIMI)/Australian Institute for Microbiology & Infection (AIMI) Associate Members
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)/Institute of Biomedical Materials and Devices (IBMD) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-12-15T23:50:35Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/182538