Stepwise increase of angiopoietin-2 serum levels is related to haemodynamic and functional impairment in stable chronic heart failure.

Abstract

BACKGROUND:

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.

METHODS AND RESULTS:

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).

CONCLUSIONS:

These data demonstrate that angiopoietin-2 and selected serum markers of angiogenesis progressively increase with haemodynamic and functional decline in CHF.

• Authors: Ermanno Eleuteri, Antonino Di Stefano, Franco Tarro Genta, Chiara Vicari, Isabella Gnemmi, Marilena Colombo, Alessandro Mezzani, Pantaleo Giannuzzi
• Journal: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology (Eur J Cardiovasc Prev Rehabil) Vol. 18 Issue 4 Pg. 607-14 (Aug 2011) ISSN: 1741-8275 [Electronic] England
• PMID: 21450636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ANGPT1 protein, human
• Angiopoietin-1
• Angiopoietin-2
• Biomarkers
• Peptide Fragments
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Receptor, TIE-2
• angiogenin
• Ribonuclease, Pancreatic

Topics

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