PXD051288-1

PXD051288 is an original dataset announced via ProteomeXchange.

Title	In vitro Modelling of Cardiovascular Damage following Hypertensive Disorders of Pregnancy using Cardiac Spheroids and Patient-derived Plasma
Description	Background: Hypertensive disorders of pregnancy (HDP) affect 2-8% of pregnancies and are associated postpartum with ongoing, increased cardiovascular disease (CVD) risk. In this study, we aimed to model HDP-induced CVD and decipher systemic mechanisms, using an advanced 3D in vitro cardiac spheroid model. Methods: Human iPSC-derived cardiomyocytes, cardiac fibroblasts and coronary artery endothelial cells were co-cultured to form cardiac spheroids (CS ) in collagen type-1 hydrogels containing 10% patient plasma collected five years postpartum (n=5 per group: normotensive control, gestational hypertension (GH) and preeclampsia). Plasma-treated CS were assessed for cell viability, contractile function and markers of cardiac damage using immunofluorescence staining and imaging. An untargeted, label-free quantitative proteomic analysis of plasma samples was conducted (controls n=24; GH n=5; preeclampsia n=13). Results: Contraction frequency (CF) was increased in preclampsia-treated CS (CF:45.5 contractions/minute, p<0.001) and GH-treated CS (CF:45.7 contractions/minute, p<0.001), compared to controls (CF=21.8 contractions/minute). Only GH-treated CS presented increased fractional shortening (FS) % (FS%=9.5%, p<0.05), compared to controls (FS%=3.7%); this was in conjunction with a reduction in cell viability by ͠ 20% (p<0.05), and an increase in α-SMA expression (p<0.05). Proteomics analysis identified twenty differentially abundant proteins, with haemoglobin A2 the only protein perturbed in both GH and preeclampsia versus control (p<0.05). Conclusions: GH-induced CVD appears linked to an increase in cell death signaling and cardiac remodeling and preeclampsia-induced CVD to vascular and endothelial cell dysfunction. CS could in future be used to assess early changes in cardiac function and as a precision medicine platform for testing post-HDP CVD prevention therapeutics.
HostingRepository	PRIDE
AnnounceDate	2024-11-25
AnnouncementXML	Submission_2024-11-24_22:02:30.688.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051288
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Matthew Padula
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-09 00:41:07	ID requested
⏵ 1	2024-11-24 22:02:31	announced

10.1186/S13293-024-00672-6;

10.6019/PXD051288;

submitter keyword: proteomics, data independent acquisition,Cardivascular disease, spheroids, ion mobility separation

Lana McClements
contact affiliation	School of Life Sciences, University of Technology Sydney
contact email	lana.mcclements@uts.edu.au
lab head
Matthew Padula
contact affiliation	University of technology Sydney
contact email	matthew.padula@uts.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051288
     1. Label: PRIDE project
     2. Name: In vitro Modelling of Cardiovascular Damage following Hypertensive Disorders of Pregnancy using Cardiac Spheroids and Patient-derived Plasma