title: 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.
  
  
  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: Divisione di Cardiologia Riabilitativa, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Veruno, Veruno (NO), Italy.
authors: Ermanno
authors: E
authors: Eleuteri
authors: Antonino
authors: A
authors: Di Stefano
authors: Franco
authors: F
authors: Tarro Genta
authors: Chiara
authors: C
authors: Vicari
authors: Isabella
authors: I
authors: Gnemmi
authors: Marilena
authors: M
authors: Colombo
authors: Alessandro
authors: A
authors: Mezzani
authors: Pantaleo
authors: P
authors: Giannuzzi
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018919:Neovascularization, Physiologic; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000097:blood; D042787:Receptor, TIE-2 / Q000097:blood; D012044:Regression Analysis; D012259:Ribonuclease, Pancreatic / Q000097:blood; D012720:Severity of Illness Index; D013318:Stroke Volume; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D016277:Ventricular Function, Left
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers; D010446:Peptide Fragments; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D042787:Receptor, TIE-2; C046366:angiogenin; D012259:Ribonuclease, Pancreatic