Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia

Richards, C; Sesperez, K; Chhor, M; Ghorbanpour, S; Rennie, C; Ming, CLC; Evenhuis, C; Nikolic, V; Orlic, NK; Mikovic, Z; Stefanovic, M; Cakic, Z; McGrath, K; Gentile, C; Bubb, K; McClements, L

Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia

Sesperez, K Chhor, M Ghorbanpour, S Rennie, C Ming, CLC Evenhuis, C Nikolic, V Orlic, NK Mikovic, Z Stefanovic, M Cakic, Z McGrath, K Gentile, C

Bubb, K McClements, L

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: Biology of Sex Differences, 2021, 12, (1), pp. 31
Issue Date:: 2021-04-20

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Field	Value	Language
dc.contributor.author	Richards, C https://orcid.org/0000-0001-5080-9164
dc.contributor.author	Sesperez, K
dc.contributor.author	Chhor, M
dc.contributor.author	Ghorbanpour, S
dc.contributor.author	Rennie, C
dc.contributor.author	Ming, CLC
dc.contributor.author	Evenhuis, C
dc.contributor.author	Nikolic, V
dc.contributor.author	Orlic, NK
dc.contributor.author	Mikovic, Z
dc.contributor.author	Stefanovic, M
dc.contributor.author	Cakic, Z
dc.contributor.author	McGrath, K
dc.contributor.author	Gentile, C https://orcid.org/0000-0002-3689-4275
dc.contributor.author	Bubb, K
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.date.accessioned	2022-01-12T07:56:06Z
dc.date.available	2021-04-07
dc.date.available	2022-01-12T07:56:06Z
dc.date.issued	2021-04-20
dc.identifier.citation	Biology of Sex Differences, 2021, 12, (1), pp. 31
dc.identifier.issn	2042-6410
dc.identifier.issn	2042-6410
dc.identifier.uri	http://hdl.handle.net/10453/153003
dc.description.abstract	BACKGROUND: Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. METHODS: The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. RESULTS: The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein expression (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). CONCLUSIONS: The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation.ispartof	Biology of Sex Differences
dc.relation.isbasedon	10.1186/s13293-021-00376-1
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.mesh	Animals
dc.subject.mesh	Collagen
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Perfusion
dc.subject.mesh	Placenta
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Pregnancy
dc.subject.mesh	Pregnancy Complications, Cardiovascular
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Rats
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Sex Characteristics
dc.subject.mesh	Tacrolimus Binding Proteins
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Placenta
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Rats
dc.subject.mesh	Rats, Sprague-Dawley
dc.subject.mesh	Pre-Eclampsia
dc.subject.mesh	Pregnancy Complications, Cardiovascular
dc.subject.mesh	Collagen
dc.subject.mesh	Tacrolimus Binding Proteins
dc.subject.mesh	RNA, Messenger
dc.subject.mesh	Perfusion
dc.subject.mesh	Pregnancy
dc.subject.mesh	Sex Characteristics
dc.subject.mesh	Female
dc.title	Characterisation of cardiac health in the reduced uterine perfusion pressure model and a 3D cardiac spheroid model, of preeclampsia
dc.type	Journal Article
utslib.citation.volume	12
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/Strength - CHT - Health Technologies
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/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-01-12T07:56:00Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	12
utslib.citation.issue	1

Abstract:

BACKGROUND: Preeclampsia is a dangerous cardiovascular disorder of pregnancy that leads to an increased risk of future cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health in preeclampsia are unknown. A novel anti-angiogenic protein, FKBPL, is emerging as having a potential role in both preeclampsia and cardiovascular disease (CVD). Therefore, in this study we aimed to characterise cardiac health and FKBPL regulation in the rat reduced uterine perfusion pressure (RUPP) and a 3D cardiac spheroid model of preeclampsia. METHODS: The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidney, liver and placenta (n ≥ 6). Picrosirius red staining was performed to quantify collagen I and III deposition in rat hearts, placentae and livers as an indicator of fibrosis. RT-qPCR was used to determine changes in Fkbpl, Icam1, Vcam1, Flt1 and Vegfa mRNA in hearts and/or placentae and ELISA to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion. Immunofluorescent staining was also conducted to analyse the expression of cardiac FKBPL. Cardiac spheroids were generated using human cardiac fibroblasts and human coronary artery endothelial cells and treated with patient plasma from normotensive controls, early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE); n = 3. FKBPL and CD31 expression was quantified by immunofluorescent labelling. RESULTS: The RUPP procedure induced significant increases in blood pressure (p < 0.001), collagen deposition (p < 0.001) and cardiac BNP45 (p < 0.05). It also induced a significant increase in cardiac FKBPL mRNA (p < 0.05) and protein expression (p < 0.01). RUPP placentae also exhibited increased collagen deposition and decreased Flt1 mRNA expression (p < 0.05). RUPP kidneys revealed an increase in average glomerular size (p < 0.05). Cardiac spheroids showed a significant increase in FKBPL expression when treated with LOPE plasma (p < 0.05) and a trend towards increased FKBPL expression following treatment with EOPE plasma (p = 0.06). CONCLUSIONS: The rat RUPP model induced cardiac, renal and placental features reflective of preeclampsia. FKBPL was increased in the hearts of RUPP rats and cardiac spheroids treated with plasma from women with preeclampsia, perhaps reflective of restricted angiogenesis and inflammation in this disorder. Elucidation of these novel FKBPL mechanisms in cardiac health in preeclampsia could be key in preventing future CVD.

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http://hdl.handle.net/10453/153003