Soluble Fms-like Tyrosine Kinase 1 Is a Novel Predictor of Brain Natriuretic Peptide Elevation

Kameda, Ryo; Yamaoka‐Tojo, Minako; Makino, Akihiro; Wakaume, Kazuki; Nemoto, Shinji; Kitasato, Lisa; Shimohama, Takao; Tojo, Taiki; Machida, Yuichiro; Izumi, Tohru

doi:10.1536/ihj.54.133

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…Thus, PlGF was significantly correlated to inflammatory markers such as hs-CRP and to natriuretic peptide and more precisely BNP [26]. A relationship between PlGF and natriuretic peptides was expected, as PlGF is required for endothelial cell and fibroblast's response to pressure overload [8,9]. Our study extends the relation between sFlt-1 and natriuretic peptides by showing a significant relation with NT-proBNP.…”

Section: Discussionsupporting

confidence: 71%

“…It was also recently reported that circulating levels of sFlt-1 and PlGF are elevated in patients with advanced coronary atherosclerosis and HF [13,14]. A paracrine role of sFlt-1 and PlGF as regulators of cardiac adaptation and hypertrophy was also suggested [8,9]. Due to their involvement in the pathogenesis of HF, sFlt-1 and PlGF might represent risk biomarkers for adverse incident CV events in this population.…”

Section: Introductionmentioning

confidence: 92%

“…The fms-like tyrosine kinase 1 (Flt-1) modulates the activity of various growth factors, such as placental growth factor (PlGF) [8,9]. Flt-1 is a transmembraneous tyrosine-kinase expressed in endothelial cells and monocytes [10].…”

Section: Introductionmentioning

confidence: 99%

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Sflt-1 in heart failure: relation with disease severity and biomarkers

Gruson

Hermans

Ferracin

et al. 2016

Scandinavian Journal of Clinical and Laboratory Investigation

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Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p < 0.01). Concentration of sFlt-1 was related to HF severity (p < 0.001) and was correlated to NT-proBNP (ρ = 0.37, p < 0.01), soluble ST2 (ρ = 0.52, p < 0.01), Galectin-3 (ρ = 0.38, p < 0.01), aldosterone (ρ = 0.25, p = 0.01) and PTH(1-84) (ρ = 0.38, p < 0.01). Furthermore, sFlt-1 levels were associated to long-term CV risk. These results suggest a potential role of sFlt-1 in HF and its potential role as biomarker of CV risk.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 92%

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Sflt-1 in heart failure: relation with disease severity and biomarkers

Gruson

Hermans

Ferracin

et al. 2016

Scandinavian Journal of Clinical and Laboratory Investigation

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“…Recently, two large meta-analyses, by McDonald et al 18 and Bellamy et al 19 , showed that women with PE have higher risks of coronary heart disease and stroke later in life. The serum concentration of sFlt-1 has been shown to be increased in individuals with acute myocardial infarction compared with those without, and it is a good predictor of development of heart failure in patients with coronary heart disease [14][15][16] . Further, in an earlier study, we showed that women with PE had thicker intima and thinner media dimensions and a higher I/M ratio compared with women with normal pregnancy, both during pregnancy and at 1 year postpartum 22 .…”

Section: Discussionmentioning

confidence: 99%

Association between angiogenic factors and signs of arterial aging in women with pre‐eclampsia

Akhter

Wikström

Larsson

et al. 2017

Ultrasound in Obstet & Gyne

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ObjectivePre‐eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt‐1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt‐1, PlGF and the sFlt‐1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.MethodsSerum sFlt‐1 and PlGF levels were measured using commercially available enzyme‐linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high‐frequency (22‐MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum.ResultsDuring pregnancy, higher levels of sFlt‐1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt‐1 and the sFlt‐1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt‐1 and the sFlt‐1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt‐1 and the sFlt‐1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum.ConclusionsHigher sFlt‐1 levels and sFlt‐1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt‐1 levels and the sFlt‐1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

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“…Goetze et al 22 found a significantly positive correlation between VEGF and BNP mRNA in an animal study. Kameda et al 23 suggested that high sVEGFR-1 levels may be an effective biomarker to predict the progression of heart failure in patients with CAD. We speculate that an increasing level of sVEGFR-1 by an increasing level of NT-proBNP may be a physiological response to heart failure, designed to decrease angiogenesis in HFrEF and HFmrEF patients, unlike the previous literature.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the effects of different treatment modalities on angiogenesis in heart failure patients with reduced/mid-range ejection fraction via VEGF and sVEGFR-1

Ertürk

Sağlam

Elasan

et al. 2018

SMJ

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Objectives:To investigate the clinical significance of VEGF, sVEGFR-1 in heart failure reduced ejection fraction (HFrEF) and heart failure mid-range ejection fraction (HFmrEF) patients.Methods:A total of 104 people consisting of HFrEF and HFmrEF patients (n=54) and healthy (n=50) subjects were included in this comparative cross-sectional study. The study took place in Gulhane Training and Research Hospital, Ankara, Turkey, between 2011 and 2013. Serum VEGF, sVEGFR-1, plasma pro-BNP analysis and transthoracic echocardiography were performed.Results:The average sVEGFR-1 level of the HFrEF and HFmrEF patients was significantly higher than the control group (0.185±0.122; 0.141±0.120; p=0.013). The average sVEGFR-1 level of the HFrEF and HFmrEF patients using beta-blocker was significantly higher than the HFrEF and HFmrEF patients not using it (p=0.015). There was a significant and positive correlation between sVEGFR-1 and N-terminal pro-brain natriuretic peptide (pro-BNP) levels in the group with HF (r=0.211, p=0.044).Conclusion:It increases awareness about the role of sVEGFR-1 in HFrEF anf HFmrEF patients and the need for further studies. Beta-blocker may have a negative effect on angiogenesis in HFrEF and HFmrEF via increasing sVEGFR-1 levels. Additionally, Pro-BNP may contribute to inhibiting angiogenesis by increasing sVEGFR-1 levels and sVEGFR-1 may be an important biomarker in HFrEF and HFmrEF.

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Soluble Fms-like Tyrosine Kinase 1 Is a Novel Predictor of Brain Natriuretic Peptide Elevation

Cited by 11 publications

References 36 publications

Sflt-1 in heart failure: relation with disease severity and biomarkers

Sflt-1 in heart failure: relation with disease severity and biomarkers

Association between angiogenic factors and signs of arterial aging in women with pre‐eclampsia

Evaluation of the effects of different treatment modalities on angiogenesis in heart failure patients with reduced/mid-range ejection fraction via VEGF and sVEGFR-1

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