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Int. J. Mol. Sci. 2017, 18(11), 2371; https://doi.org/10.3390/ijms18112371

Increased Serum Levels of Fetal Tenascin-C Variants in Patients with Pulmonary Hypertension: Novel Biomarkers Reflecting Vascular Remodeling and Right Ventricular Dysfunction?

1
Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, Jena University Hospital, Friedrich-Schiller-University, 07747 Jena, Germany
2
Department of Internal Medicine II, Division of Cardiology, Elisabeth Klinikum Schmalkalden, 98574 Schmalkalden, Germany
3
Department of Cardiology, Charité–Universitätsmedizin Berlin, 12203 Berlin, Germany
4
Department of Internal Medicine, Division of Cardiology, University Hospital Düsseldorf, Heinrich Heine University, 40225 Düsseldorf, Germany
5
Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany
*
Author to whom correspondence should be addressed.
Received: 8 October 2017 / Revised: 31 October 2017 / Accepted: 4 November 2017 / Published: 8 November 2017
(This article belongs to the Special Issue Extracellular Matrix in Development and Disease)
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Abstract

Pulmonary vascular remodeling is a pathophysiological feature that common to all classes of pulmonary hypertension (PH) and right ventricular dysfunction, which is the major prognosis-limiting factor. Vascular, as well as cardiac tissue remodeling are associated with a re-expression of fetal variants of cellular adhesion proteins, including tenascin-C (Tn-C). We analyzed circulating levels of the fetal Tn-C splicing variants B+ and C+ Tn-C in serum of PH patients to evaluate their potential as novel biomarkers reflecting vascular remodeling and right ventricular dysfunction. Serum concentrations of B+ and C+ Tn-C were determined in 80 PH patients and were compared to 40 healthy controls by enzyme-linked immunosorbent assay. Clinical, laboratory, echocardiographic, and functional data were correlated with Tn-C levels. Serum concentrations of both Tn-C variants were significantly elevated in patients with PH (p < 0.05). Significant correlations could be observed between Tn-C and echocardiographic parameters, including systolic pulmonary artery pressure (B+ Tn-C: r = 0.31, p < 0.001, C+ Tn-C: r = 0.26, p = 0.006) and right atrial area (B+ Tn-C: r = 0.46, p < 0.001, C+ Tn-C: r = 0.49, p < 0.001), and laboratory values like BNP (B+ Tn-C: r = 0.45, p < 0.001, C+ Tn-C: r = 0.42, p < 0.001). An inverse correlation was observed between Tn-C variants and 6-minute walk distance as a functional parameter (B+ Tn-C: r = −0.54, p < 0.001, C+ Tn-C: r = −0.43, p < 0.001). In a multivariate analysis, B+ Tn-C, but not C+ Tn-C, was found to be an independent predictor of pulmonary hypertension. Both fetal Tn-C variants may represent novel biomarkers that are capable of estimating both pulmonary vascular remodeling and right ventricular load. The potential beneficial impact of Tn-C variants for risk stratification in patients with PH needs further investigation. View Full-Text
Keywords: fetal tenascin-C; pulmonary hypertension; vascular remodeling; right ventricular dysfunction fetal tenascin-C; pulmonary hypertension; vascular remodeling; right ventricular dysfunction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rohm, I.; Grün, K.; Müller, L.M.; Kretzschmar, D.; Fritzenwanger, M.; Yilmaz, A.; Lauten, A.; Jung, C.; Schulze, P.C.; Berndt, A.; Franz, M. Increased Serum Levels of Fetal Tenascin-C Variants in Patients with Pulmonary Hypertension: Novel Biomarkers Reflecting Vascular Remodeling and Right Ventricular Dysfunction? Int. J. Mol. Sci. 2017, 18, 2371.

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