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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Aims Circulating biomarkers are commonly used in diagnosis and prognosis of heart failure with preserved ejection fraction (HFpEF) in clinical practice. However, the diagnostic and prognostic potential of current biomarkers in HFpEF remain unclear. Methods and results We conducted a search of the PubMed, Web of Science, MEDLINE and SCOPUS (1900 to January 2020) databases of all diagnostic (n=1,104) and prognostic (n=53,497) biomarkers investigated in people with HFpEF. B-type natriuretic peptide (BNP) displayed satisfactory sensitivity (0.81, 95% CI: 0.76 to 0.85; I2=0) and specificity (0.86, 95% CI: 0.82 to 0.89; I2=16.9%) for the diagnosis of HFpEF. Natriuretic peptides (NPs), including N-terminal pro BNP (NT-proBNP) and BNP, were associated with over two-fold increased risk of mortality (NT-proBNP: HR=2.27, 95% CI: 1.69 to 3.06, I2=87.6%; BNP: HR=3.01, 95% CI: 1.27 to 7.21, I2=97.2%), hospitalisation (NT-proBNP: HR=3.54, 95% CI: 2.83 to 4.43, I2=83.4%), and a composite event of both (NT-proBNP: HR=2.55, 95% CI: 2.13 to 3.05, I2=78.1%; BNP: HR=2.28, 95% CI: 1.42 to 3.69, I2=75.8%) in people with HFpEF. Interestingly, Galectin-3 (Gal-3) (sensitivity: 0.70, 95% CI: 0.63 to 0.75, I2=86.7%; specificity: 0.78, 95% CI: 0.69 to 0.85, I2=68.6%) and soluble suppression of tumorigenicity 2 (sST2) (sensitivity: 0.58, 95% CI: 0.52 to 0.64, I2=88.1%; specificity: 0.59, 95% CI: 0.49 to 0.68, I2=69.5%) showed limited diagnostic potential of HFpEF. Conclusion Amongst currently available biomarkers, BNP remains the most reliable diagnostic marker of HFpEF. Although there was high heterogeneity between the studies included, BNP or NT-proBNP could also have promising prognostic potential in HFpEF.

Aims:The aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease.We aim to discuss the biomarkers' pathophysiological roles as a reflection of the cardiac remodelling mechanisms in the presence of DM. Methods:We performed the literature search to include studies from 2003 to 2021 using the following databases: MEDLINE, Scopus, Web of Science, PubMed, and Cochrane library. Articles that met our inclusion criteria were screened and appraised before being included in this review. The PRISMA guidelines for Scoping Reviews were followed. Results:Our literature search identified a total of 43 eligible articles, which were included in this scoping review. We identified 15 different biomarkers, each described by at least two studies, that were used to determine signs of cardiac remodelling in cardiovascular disease (CVD) and people with DM. NT-proBNP was identified as the most frequently employed biomarker in this context; however, we also identified emerging biomarkers including hs-CRP, hs-cTnT, and Galectin-3. Conclusion:There is a complex relationship between DM and cardiovascular health, where more research is needed. Current biomarkers reflective of adverse cardiac remodelling in DM are often used to diagnose other CVDs, such as NT-proBNP for heart failure. Hence there is a need for identification of specific biomarkers that can detect early signs of cardiac remodelling in the presence of DM. Further research into these biomarkers and mechanisms can deepen our understanding of their role in DM-associated CVD and lead to better preventative therapies.

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.