Article

Serum syndecan-4 is a novel biomarker for patients with chronic heart failure.

Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Journal of Cardiology (Impact Factor: 2.3). 03/2011; 57(3):325-32. DOI: 10.1016/j.jjcc.2011.01.012
Source: PubMed

ABSTRACT Syndecan-4 is a transmembrane heparan sulfate-carrying glycoprotein that mediates signal transduction pathways activated by growth factors and cell surface receptors, thereby modulating tissue regeneration, angiogenesis, and focal adhesion. The aim of the present study was to determine the clinical use of serum syndecan-4 concentration for diagnosis of heart failure.
Concentration of serum syndecan-4 and other biomarkers of heart failure was measured in 45 patients with heart failure and 21 healthy subjects. Clinical and echocardiographic parameters of cardiac function were recorded.
Serum syndecan-4 concentration significantly increased in proportion to the decrease in ejection fraction (r=-0.599, p<0.001) and increase in the left ventricular (LV) mass index (r=0.315, p<0.05). Serum syndecan-4 concentration was significantly correlated with LV geometrical parameters (i.e. LV mass index, LV end-diastolic volume, and LV dimension), while B-type natriuretic peptide (BNP) was significantly correlated with pressure-related parameters [i.e. early transmitral flow velocity/early diastolic velocity of the mitral valve annulus (E/e'), right ventricular systolic pressure, and left atrial volume index]. Syndecan-4 concentration did not significantly correlate with plasma BNP, transforming growth factor-1, matrix metalloproteinase-2, and tenascin-C concentrations. Serum syndecan-4 concentration could predict cardiac death and re-hospitalization due to heart failure (area under curve, 0.706, p<0.05).
Serum syndecan-4 concentration shows promise as a novel diagnostic and prognostic biomarker for heart failure. Since syndecan-4 correlated with LV geometrical rather than hemodynamic parameters, serum syndecan-4 may represent a biomarker of LV remodeling in the failing heart.

0 Bookmarks
 · 
100 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: We set out to evaluate the utility of selected heart failure (HF) biomarkers in patients with dilated cardiomyopathy (DCM). METHODS: In a prospective, randomized study, 68 DCM patients with left ventricular ejection fraction (LVEF) ≤40% treated optimally were included. They were observed for 5years. Initial and control tests included full clinical examination, measurement of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and IL-10, syndecan-4, cystatin C (CysC) and N-terminal pro-brain natriuretic peptide (NT-proBNP), echocardiographic examination, and the assessment of exercise capacity in 6-minute walk test (6MWT). RESULTS: Finally, after 5-year follow-up we analyzed the data of 45 DCM patients. Concentration of syndecan-4 correlated negatively with LVEF (R=-0.36, p=0.02) and positively with LV systolic (R=0.57, p<0.001) and diastolic diameters (R=0.64, p<0.001). A positive correlation between CysC and right ventricular diastolic diameter (R=0.38, p=0.01), and negative correlations between CysC and glomerular filtration rate (R=-0.49, p<0.001), LVEF (R=-0.4, p=0.02), and 6MWT (R=-0.46, p<0.001) were noted. Patients who had an increase in LVEF during 5years were characterized by lower levels of CysC (p=0.01) and NT-proBNP (p<0.001). CysC≤95mg/l and NT-proBNP≤32pg/ml were the best predictors of LVEF increase in DCM patients. Multivariate regression analysis showed that 6MWT was the only independent predictor of HF re-hospitalization (OR 0.989; p<0.001), and NT-proBNP and LV diastolic diameter were the only risk factors of increased mortality (OR 1.001; p=0.007 and OR 2.960; p=0.025, respectively) in DCM patients. CONCLUSIONS: CysC correlates negatively with both kidney function and exercise capacity. Syndecan-4 may be a useful biomarker for predicting adverse LV remodeling in DCM patients.
    International journal of cardiology 02/2013; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In contrast to public perception, the morbidity and mortality and the resultant healthcare costs associated with chronic heart failure (HF) are increasing and arguably reaching epidemic proportions. Although basic research efforts have provided unique insights into fundamental processes that govern myocardial extracellular matrix (ECM) growth and function, the translation of these findings to improved diagnostics and therapeutics for HF has not been as forthcoming. The factors that contribute to this relative paucity of new clinical tools for HF are multifactorial but likely include the need to recognize and differentiate HF phenotypes and to couple the use of biomarkers and multimodality imaging in early translational research studies. Recognizing the classification scheme of HF with a reduced ejection fraction (EF) to that of HF with a preserved EF and incorporating unique and differential measurements of ECM remodeling to these specific disease processes are warranted. For example, profiling pathways of ECM degradation such as the matrix metalloproteinases in patients with ischemic heart disease and HF with a reduced EF can provide prognostic information in terms of risk of progression to HF. In patients with chronic hypertensive disease and HF with a preserved EF, plasma profiling indexes of ECM synthesis and turnover, as well as advances in ECM imaging, have been shown to provide diagnostic and prognostic use. In terms of therapeutics, strategies to stabilize the ECM in HF with a reduced EF hold potential, whereas in contradistinction, selective antifibrotic agents may hold promise for HF with a preserved EF. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00946231.
    Circulation Research 08/2013; 113(6):725-38. · 11.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth factors. The sulfation pattern of the heparan sulfate chains is a critical regulatory step affecting the binding of chemokines and growth factors. N-deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze sulfation. Previously published work has shown that HSPGs alter tangent moduli and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth muscle would lead to significant changes in heparan sulfate modification and the elastic properties of arteries. In line with this hypothesis, the axial tangent modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth muscle (SM22αcre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial tangent modulus was associated with a significant switch in myosin and actin types and isoforms expressed in aorta and isolated aortic vascular smooth muscle cells. In contrast, no changes were found in the compliance of smaller thoracodorsal arteries of SM22αcre(+)Ndst1(-/-) mice. In summary, the major findings of this study were that targeted ablation of Ndst1 in smooth muscle cells results in altered biomechanical properties of aorta and differential expression of myosin and actin types and isoforms.
    Molecular and Cellular Biochemistry 10/2013; · 2.33 Impact Factor

Full-text (2 Sources)

Download
39 Downloads
Available from
May 29, 2014