The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure

AbstractObjectiveThe aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure.Methods and resultsPlasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p<0.01). N-terminal pro-brain natriuretic peptide and left ventricular end-diastolic dimension were positively correlated with plasma N-terminal connective tissue growth factor levels (r=0.364, p=0.006; r=0.308, p=0.016), whereas there was a negative correlation between left ventricular ejection fraction and plasma N-terminal connective tissue growth factor (r=−0.353, p=0.005). Connective tissue growth factor was significantly correlated with the severity of heart failure (p<0.001). Moreover, addition of connective tissue growth factor to N-terminal pro-brain natriuretic peptide did not significantly increase area under curve for diagnosing heart failure (area under curve difference 0.031, p>0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices.ConclusionsPlasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

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Connective Tissue Growth Factor Inhibition Attenuates Left Ventricular Remodeling and Dysfunction in Pressure Overload–Induced Heart Failure

Hypertension ◽

10.1161/hypertensionaha.114.03279 ◽

2014 ◽

Vol 63 (6) ◽

pp. 1235-1240 ◽

Cited By ~ 47

Author(s):

Zoltán Szabó ◽

Johanna Magga ◽

Tarja Alakoski ◽

Johanna Ulvila ◽

Jarkko Piuhola ◽

...

Keyword(s):

Heart Failure ◽

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Pressure Overload ◽

Left Ventricular ◽

Tissue Growth

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Abstract 19273: Fibroblast-Derived TSP1, via CD47, Upregulates Connective Tissue Growth Factor to Promote Left Ventricular Fibrosis and Heart Failure

Circulation ◽

10.1161/circ.130.suppl_2.19273 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Maryam Sharifi-Sanjani ◽

Kevin Beezhold ◽

Hallie Cook ◽

Jeffrey Baust ◽

Jeffrey Isenberg

Keyword(s):

Heart Failure ◽

Growth Factor ◽

Connective Tissue ◽

Connective Tissue Growth Factor ◽

The United States ◽

Left Ventricular ◽

Cardiac Fibroblast ◽

Tissue Growth ◽

Cell Surface Receptor ◽

Wild Type

Background: An estimated 5.5 million individuals in the United States have left ventricular heart failure (LV HF). Therapeutics, while relieving symptoms and extending life in some cases, cannot resolve this process. LV HF is characterized by excessive accumulation of the extracellular matrix. The causes of this process remain incompletely understood. Our team has recently described a widely expressed cell surface receptor CD47 that is activated by its high affinity ligand, thrombospondin-1 (TSP1) to promote LV HF. However, the role of TSP1-CD47 signaling in promoting fibrosis, in general, and in the setting of LV HF, in specific, is unknown. Methods: Wild type mice expressing CD47 and mutated mice lacking CD47 (CD47 null) were subjected to transverse aortic constriction (TAC) for 4 weeks followed by open chest pressure-volume loop analysis of cardiac hemodynamics. Signal transduction was confirmed in isolated left ventricles (LV) and normal human ventricular fibroblast cell culture systems. Results: In biopsy samples from failing human hearts and in pre-clinical model of TAC-driven LV HF, TSP1-CD47 signaling was altered. Post-TAC wild type (CD47+/+) mice developed cardiac fibrosis, associated cardiac stiffness and HF. In contrast, CD47 null mice subjected to TAC showed enhanced cardiac function and decreased fibrosis concordant with suppression of TSP1. In cardiac resident fibroblasts, but not myocytes, hypoxia rapidly induced TSP1 protein, while treating with 7N3, a TSP1-based peptide mimetic that selectively binds CD47, increased connective tissue growth factor (CTGF) protein. Further, treating cardiac fibroblast with 7N3 increased fibroblast collagen production. Finally, CD47 blocking antibody mitigated established TAC-driven LV fibrosis and HF. Conclusion: These data identify a proximate role for activated cardiac fibroblast CD47 in promoting LV fibrosis associated with HF and suggest possible therapeutic opportunity.

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Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure

Cardiology ◽

10.1159/000499179 ◽

2019 ◽

Vol 143 (3-4) ◽

pp. 77-84 ◽

Cited By ~ 4

Author(s):

Hongjie Chi ◽

Haijun Feng ◽

Xiangyu Shang ◽

Jie Jiao ◽

Lanlan Sun ◽

...

Keyword(s):

Heart Failure ◽

Growth Factor ◽

Connective Tissue ◽

Diastolic Dysfunction ◽

Connective Tissue Growth Factor ◽

Transforming Growth Factor ◽

Diastolic Heart Failure ◽

Left Ventricular ◽

Tissue Growth ◽

Tgf Β1

Background: Connective tissue growth factor (CTGF) and transforming growth factor β1 (TGF-β1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-β1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). Methods: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-β1, and B-type natriuretic peptide (BNP) were determined. Results: The plasma CTGF and TGF-β1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-β1 levels were correlated with echocardiographic parameter E/e’ and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. Conclusions: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

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