angiogenin and Heart-Failure

Topics: Aged; Biomarkers; Case-Control Studies; Coronary Disease; Cross-Sectional Studies; Female; Heart Failure; Humans; Male; Middle Aged; Ribonuclease, Pancreatic; Stroke Volume

Characteristics of heart failure with preserved ejection fraction (HFPEF) have not yet been fully understood. The objectives of this pilot study are to detect protein expression profile in the sera of HFPEF patients, and to identify potential biomarkers for the disease. Five hundred and seven proteins were detected in the sera of healthy volunteers and patients with either HFPEF or hypertension using antibody microarrays (three in each group). The results showed that the serum concentrations of 17 proteins (e.g. angiogenin, activin A and artemin) differed considerably between HFPEF and non-HFPEF patients (hypertensive patients and healthy controls), while a protein expression pattern distinct from that in non-HFPEF patients was associated with HFPEF patients. The up-regulation of angiogenin in both HFPEF patients with LVEF ≥50% (P = 0.004) and a subset of HFPEF patients with LVEF = 41-49% (P < 0.001) was further validated in 16 HFPEF patients and 16 healthy controls. Meanwhile, angiogenin distinguished HFPEF patients from controls with a mean area under the receiver operating characteristic curve of 0.88 (P < 0.001) and a diagnostic cut-off point of 426 ng/ml. Moreover, the angiogenin levels in HFPEF patients were positively correlated with Lg(N-terminal pro-B-type natriuretic peptide, NT-proBNP) (P < 0.001). In addition, high angiogenin level (≥426 ng/ml) was a predictor of all-cause death within a short-term follow-up duration, but not in the longer term of 36 months. This pilot study indicates that the aforementioned 17 potential biomarkers, such as angiogenin, may hold great promise for both diagnosis and prognosis assessment of HFPEF.

Topics: Adult; Aged; Biomarkers; Female; Gene Expression Regulation; Heart Failure; Humans; Male; Middle Aged; Pilot Projects; Prognosis; Ribonuclease, Pancreatic; Stroke Volume; Ventricular Function, Left

A reciprocal link between inflammation, oxidative/nitrosative stress, and endothelial dysfunction has been postulated in chronic heart failure (CHF). The endothelial repair mechanisms involved remain to be determined. Our aim was to investigate whether there are detectable signs of ongoing angiogenesis in serum of CHF patients and to evaluate the correlation with indexes of haemodynamic and functional impairment.. Enzyme-linked immunosorbent assay tests were used to quantify angiogenin, angiopoietin-1, angiopoietin-2, vascular endothelial growth factor, Tie-2, and brain natriuretic peptide in serum of 87 patients with CHF of increasing severity according to New York Heart Association (NYHA; class I, n = 8; II, n = 45; and III, n = 34) and in 14 healthy subjects matched for age and sex. Angiogenin, angiopoietin-2, and Tie-2 were significantly increased in CHF of increasing severity (Kruskal-Wallis: p = 0.0004, p < 0.0001, and p = 0.017, respectively). Angiopoietin-2 was inversely correlated with the 6-min walking test (r = -0.65, p < 0.0001), peak oxygen consumption (VO(2max); r = -0.57, p = 0.0002), and deceleration time (r = -0.61, p < 0.0001). Multiple regression analysis showed that angiopoietin-2 was mainly associated with VO(2max) (p = 0.018). The angiopoietin-2 area under the receiver operating characteristic curve for CHF diagnosis was 0.94 (95% CI 0.88-0.99; p < 0.001).. These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF.

Topics: Aged; Analysis of Variance; Angiopoietin-1; Angiopoietin-2; Biomarkers; Case-Control Studies; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Hemodynamics; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Neovascularization, Physiologic; Oxygen Consumption; Peptide Fragments; Receptor, TIE-2; Regression Analysis; Ribonuclease, Pancreatic; Severity of Illness Index; Stroke Volume; Up-Regulation; Vascular Endothelial Growth Factor A; Ventricular Function, Left

Patients with coronary artery disease (CAD) and left ventricular systolic dysfunction (LVSD) are often asymptomatic. Angiogenesis is implicated in the physiology of vascular repair and cardiac remodelling, and is one of many pathophysiological processes implicated in heart failure. We hypothesized that plasma indices associated with angiogenesis [angiogenin, vascular endothelial growth factor (VEGF), and angiopoietin (Ang)-1 and Ang-2] would be abnormal in CAD patients with LVSD, being correlated with EF and wall motion abnormalities (wall motion score) independently of underlying CAD (coronary atheroma score). We also evaluated the specificity of angiogenic 'biomarkers' in their detection of LVSD [ejection fraction (EF) <40%] amongst CAD patients.. Using a cross sectional approach, we measured angiogenin, VEGF, Ang-1 and Ang-2 by ELISA in 194 CAD patients (aged 34-81 years) undergoing elective coronary angiography.. Levels of angiogenin were inversely related with EF (r = -0.17, P = 0.02) and positively with coronary atheroma scores (r = 0.15, P = 0.04, but not independently of EF). Other angiogenic markers were unrelated to objective measures of LVSD but VEGF (P = 0.008) and Ang-2 (P = 0.015) were lower amongst those patients with heart failure. Angiogenin levels were related to wall motion scores (r = 0.16, P = 0.024).. Heart failure has a modest impact on biomarkers of angiogenesis, in patients with CAD. Further research is warranted into the diagnostic and prognostic utility of biomarkers of angiogenesis, in this common cardiac condition.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Angiopoietin-1; Angiopoietin-2; Biomarkers; Coronary Angiography; Coronary Artery Disease; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Middle Aged; Neovascularization, Pathologic; Ribonuclease, Pancreatic; Stroke Volume; Vascular Endothelial Growth Factor A; Ventricular Dysfunction, Left

Abnormal indices of angiogenesis have been reported in chronic heart failure (CHF). We tested the hypothesis that circulating angiogenin (a potent inducer of neovascularization in vivo) is higher in CHF patients compared with controls and associated with indices of CHF severity: brain natriuretic peptide (BNP), Simpson's left ventricular ejection fraction (EF), and New York Heart Association (NYHA) class.. Using a cross-sectional approach, we measured serum angiogenin and BNP levels in 109 consecutive patients with CHF (85 males; mean age 60 (standard deviation (SD) 10 yrs) and 112 asymptomatic controls with normal cardiac function and related levels to echocardiographic parameters.. Angiogenin was significantly higher in CHF patients compared to controls (P < 0.001). On univariate analysis, angiogenin was positively associated with age, plasma glucose, insulin, and BNP (all P < 0.001); and negatively correlated with diastolic blood pressure (P = 0.04) and EF (P = 0.002). Angiogenin levels increased in an ordinal fashion with NYHA class, exaggerated by the presence of diabetes mellitus (pseudo R2 = 0.15, P < 0.001). In multivariate analysis, angiogenin levels were only associated with deteriorating NYHA classification (beta = 0.14 (95% confidence interval (CI) 0.09-0.19), P < 0.001). Angiogenin was also a modest discriminator for the presence of CHF (area under the curve 0.72; 95% CI 0.62-0.82), P < 0.001).. Angiogenin is related to worsening heart failure severity (NYHA classification), with the highest levels in NYHA class III. Further research is warranted to determine the validity of angiogenin in a diagnostic and prognostic capacity in CHF.

Topics: Aged; Area Under Curve; Biomarkers; Case-Control Studies; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ribonuclease, Pancreatic; Severity of Illness Index