Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Ding, Lan; Chuanming, Bai; Liu, Ying

doi:10.1590/1414-431x20186921

Cited by 8 publications

(6 citation statements)

References 29 publications

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“…This cardiac remodelling and fibrosis is likely driven by inflammation, as shown in published literature [ 60 ], and inflammation is a common feature of both EOPE and LOPE [ 61 ]. We have noted a significant increase in cardiac levels of BNP, which is indicative of diastolic dysfunction and cardiac hypertrophy that is supported by other studies’ findings in preeclampsia models [ 59 , 62 ].…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2021

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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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Section: Discussionsupporting

confidence: 90%

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

et al. 2021

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“…BNP is released from the cardiac ventricles in response to diastolic and systolic dysfunction, which places additional stress on the heart walls [58,59]. We have noted a signi cant increase in cardiac levels of BNP, which is supported by other studies' ndings in preeclampsia models [57,60].…”

Section: Discussionsupporting

confidence: 86%

Characterisation of Cardiac Health in the Reduced Uterine Perfusion Pressure Model and a 3D Cardiac Spheroid Model, of Preeclampsia

Richards

Sesperez

Chhor

et al. 2020

Preprint

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Background: Preeclampsia is a life-threatening cardiovascular disorder of pregnancy that leads to an increased risk of ongoing cardiovascular and metabolic disorders. Much of the pathogenesis and mechanisms involved in cardiac health 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 investigate the role of FKBPL in cardiac health in the rat reduced uterine perfusion pressure (RUPP) model and 3D cardiac spheroid model, of preeclampsia.Methods: The RUPP model was induced in pregnant rats and histological analysis performed on the heart, kidneys, liver and placenta (n≥6). Picrosirius red staining was performed to quantify collagen I/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/or Vegfa mRNA in hearts and/or placentae and ELISA was used to evaluate cardiac brain natriuretic peptide (BNP45) and FKBPL secretion in rat hearts. Cardiac spheroids were generated using human cardiac fibroblasts (HCFs) and human coronary artery endothelial cells (HCAECs) 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 increase in blood pressure (p<0.001), cardiac collagen deposition (p<0.001) and cardiac BNP45 (p<0.05). It also induced a significant increase in cardiac FKBPL mRNA expression (p<0.05) and protein levels (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 patient 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 in humans. FKBPL was increased in the hearts of RUPP rats and in cardiac spheroids treated with plasma from women with preeclampsia, reflective of restricted angiogenesis in this disorder. Elucidation of this novel FKBPL mechanism in cardiac health in preeclampsia could be key in preventing future CVD.

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“…Increased circulating levels of ANP and BNP were described in PE patients, including those with reported impaired GLS [ 15 , 71 , 72 , 73 ]. Likewise, we and others found elevated ANP and BNP levels in the circulation and/or heart tissue of RUPP rats [ 52 , 74 , 75 ]. Previous studies demonstrated that activin A overexpression increases, whereas inhibition of ActIIR signaling following pressure overload or myocardial infarction decreases cardiac gene expression of both ANP and BNP in mice [ 62 , 63 ].…”

Section: Discussionsupporting

confidence: 79%

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction

Bakrania

Palei

Bhattarai

et al. 2022

Cells

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Mediators of cardiac injury in preeclampsia are not well understood. Preeclamptic women have decreased cardiac global longitudinal strain (GLS), a sensitive measure of systolic function that indicates fibrosis and tissue injury. GLS is worse in preeclampsia compared to gestational hypertension, despite comparable blood pressure, suggesting that placental factors may be involved. We previously showed that Activin A, a pro-fibrotic factor produced in excess by the placenta in preeclampsia, predicts impaired GLS postpartum. Here, we hypothesized that chronic excess levels of Activin A during pregnancy induces cardiac dysfunction. Rats were assigned to sham or activin A infusion (1.25–6 µg/day) on a gestational day (GD) 14 (n = 6–10/group). All animals underwent blood pressure measurement and comprehensive echocardiography followed by euthanasia and the collection of tissue samples on GD 19. Increased circulating activin A (sham: 0.59 ± 0.05 ng/mL, 6 µg/day: 2.8 ± 0.41 ng/mL, p < 0.01) was associated with impaired GLS (Sham: −22.1 ± 0.8%, 6 µg/day: −14.7 ± 1.14%, p < 0.01). Activin A infusion (6 µg/day) increased beta-myosin heavy chain expression in heart tissue, indicating cardiac injury. In summary, our findings indicate that increasing levels of activin A during pregnancy induces cardiac dysfunction and supports the concept that activin A may serve as a possible mediator of PE-induced cardiac dysfunction.

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Interleukin-6 contributes to myocardial damage in pregnant rats with reduced uterine perfusion pressure

Cited by 8 publications

References 29 publications

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

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

Characterisation of Cardiac Health in the Reduced Uterine Perfusion Pressure Model and a 3D Cardiac Spheroid Model, of Preeclampsia

Sustained Elevated Circulating Activin A Impairs Global Longitudinal Strain in Pregnant Rats: A Potential Mechanism for Preeclampsia-Related Cardiac Dysfunction

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