Plasma stem cell factor levels are associated with risk of cardiovascular disease and death

Björkbacka, Harry; Mattisson, Ingrid Yao; Wigren, Maria; Melander, Olle; Fredrikson, Gunilla Nordin; Bengtsson, Eva; Gonçalves, Isabel; Almgren, Peter; Lagerstedt, Jens O.; Orho‐Melander, Marju; Engström, Gunnar; Nilsson, Jan

doi:10.1111/joim.12675

Cited by 33 publications

(27 citation statements)

References 53 publications

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“…Patients with diabetes expressed lower levels of SCF. Supporting our findings, lower levels of SCF have also been associated with increased rate of coronary events and all-cause death 35,36 . Contrary to our findings, CXCL-1 levels have been found to be elevated in patients with diabetes mellitus 37,38 .…”

Section: Diabetessupporting

confidence: 87%

Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case–control analyses

Ferreira¹,

Pizard²,

Machu³

et al. 2019

Clin Res Cardiol

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HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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Section: Diabetessupporting

confidence: 87%

Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case–control analyses

Ferreira¹,

Pizard²,

Machu³

et al. 2019

Clin Res Cardiol

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“…Noteworthy, SCF levels were low before HT, following an increase after HT towards controls' levels. This may support that low plasma levels of SCF are associated with increased cardiovascular disease and mortality [45].…”

Section: Tablementioning

confidence: 56%

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Ahmed

Säleby

et al. 2020

Heart Vessels

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Receptor tyrosine kinases (RTKs) are implicated in cardiovascular growth and remodelling. We aimed to identify the plasma levels of RTKs and related proteins and their association with haemodynamic alterations in heart failure (HF) and related pulmonary hypertension (PH) following heart transplantation (HT). Using proximity extension assay, 28 RTKs and related proteins were analysed in plasma from 20 healthy controls and 26 HF patients before and 1-year after HT. In end-stage HF, out of 28 RTKs, plasma vascular endothelial growth factor-D (VEGF-D) and human epidermal growth factor-4 (HER4) were elevated compared to controls (p < 0.001), but decreased (p < 0.0001) and normalised after HT. Following HT, plasma changes (Δ) of VEGF-D correlated with Δmean pulmonary artery pressure (r s = 0.65, p = 0.00049), Δpulmonary artery wedge pressure (r s = 0.72, p < 0.0001), Δpulmonary arterial compliance (PAC) (r s = − 0.52, p = 0.0083) and Δpulmonary vascular resistance (PVR) (r s = 0.58, p = 0.0032). ΔHER4 correlated with Δmean right atrial pressure (r s = 0.51, p = 0.012), ΔNT-proBNP (r s = 0.48, p = 0.016) and Δcardiac index (r s = − 0.56, p = 0.0044). In HF patients following HT, normalisation of VEGF-D reflected reversal of passive pulmonary congestion and restored PAC and PVR; whereas the normalisation of HER4 reflected decreased volume overload and improved cardiac function. The precise function of these proteins, their potential clinical use and pathophysiological relation in HF and related PH remain to be elucidated.

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“…Additionally, low plasma SCF is reported in patients with other cardiovascular diseases and is associated with increased risk of cardiovascular events and death [ 16 , 24 ]. While SCF may be affected by other cardiovascular comorbidities present in our study population, its correlation to several PAH-related parameters, together with the research previously done on c-Kit in pulmonary hypertension, point towards a role for this protein in pulmonary arterial remodelling.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, although the role for stem cell factor (SCF), a ligand for the receptor tyrosine kinase c-Kit [ 15 ], remains unclear in pulmonary hypertension, c-Kit + progenitor cells are known to accumulate in remodelled vessels in PAH [ 9 ]. However, high plasma SCF has been shown to be associated with a lower risk of cardiovascular events and death [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Low plasma stem cell factor combined with high transforming growth factor-α identifies high-risk patients in pulmonary arterial hypertension

Bouzina

Rådegran

2018

ERJ Open Res

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In pulmonary arterial hypertension (PAH), severe vasoconstriction and remodelling of small pulmonary arteries result in high mortality. Receptor tyrosine kinases and their ligands, such as transforming growth factor (TGF)-α, modulate proliferation in PAH. Although the receptor tyrosine kinase c-Kit has been shown to be overexpressed in PAH, the expression and role of its ligand stem cell factor (SCF) remain unknown. However, low plasma SCF levels are known to be linked to higher cardiovascular mortality risk.Using proximity extension assays, we measured SCF and TGF-α in venous plasma from treatment-naïve PAH patients and healthy controls. Patients were stratified into risk classes based on PAH guidelines.Plasma SCF was decreased (p=0.013) and TGF-α was increased (p<0.0001) in PAH patients compared to controls. SCF correlated to pulmonary vascular resistance (r=−0.66, p<0.0001), cardiac index (r=0.66, p<0.0001), venous oxygen saturation (r=0.47, p<0.0008), mean right atrial pressure (r=−0.44, p<0.002) and N-terminal pro-brain natriuretic protein (r=−0.39, p<0.006). SCF was lower in “high-risk” compared to “intermediate-risk” (p=0.0015) or “low-risk” (p=0.0009) PAH patients. SCF and TGF-α levels combined (SCF/TGF-α) resulted in 85.7% sensitivity and 81.5% specificity for detecting high-risk patients (p<0.0001). Finally, REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) risk scores in PAH patients correlated to SCF/TGF-α levels (r=−0.50, p=0.0003).In conclusion, low plasma SCF combined with high TGF-α identifies high-risk PAH patients at baseline. Lower circulating SCF levels, which are associated with worse haemodynamics, may be related to the c-Kit accumulation previously observed in PAH.

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Plasma stem cell factor levels are associated with risk of cardiovascular disease and death

Abstract: This prospective population-based study demonstrates that subjects with high levels of SCF have a lower risk of cardiovascular events and death. The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity.

Cited by 33 publications

References 53 publications

Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case–control analyses

Plasma protein biomarkers and their association with mutually exclusive cardiovascular phenotypes: the FIBRO-TARGETS case–control analyses

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Low plasma stem cell factor combined with high transforming growth factor-α identifies high-risk patients in pulmonary arterial hypertension

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