PMID- 21450636 OWN - NLM STAT- MEDLINE DCOM- 20120206 LR - 20151119 IS - 1741-8275 (Electronic) IS - 1741-8267 (Linking) VI - 18 IP - 4 DP - 2011 Aug TI - Stepwise increase of angiopoietin-2 serum levels is related to haemodynamic and functional impairment in stable chronic heart failure. PG - 607-14 LID - 10.1177/1741826710389410 [doi] AB - 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. FAU - Eleuteri, Ermanno AU - Eleuteri E AD - Divisione di Cardiologia Riabilitativa, Fondazione Salvatore Maugeri, IRCCS, Istituto Scientifico di Veruno, Veruno (NO), Italy. FAU - Di Stefano, Antonino AU - Di Stefano A FAU - Tarro Genta, Franco AU - Tarro Genta F FAU - Vicari, Chiara AU - Vicari C FAU - Gnemmi, Isabella AU - Gnemmi I FAU - Colombo, Marilena AU - Colombo M FAU - Mezzani, Alessandro AU - Mezzani A FAU - Giannuzzi, Pantaleo AU - Giannuzzi P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110211 PL - England TA - Eur J Cardiovasc Prev Rehabil JT - 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 JID - 101192000 RN - 0 (ANGPT1 protein, human) RN - 0 (Angiopoietin-1) RN - 0 (Angiopoietin-2) RN - 0 (Biomarkers) RN - 0 (Peptide Fragments) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (pro-brain natriuretic peptide (1-76)) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - EC 2.7.10.1 (Receptor, TIE-2) RN - EC 3.1.27.- (angiogenin) RN - EC 3.1.27.5 (Ribonuclease, Pancreatic) SB - IM MH - Aged MH - Analysis of Variance MH - Angiopoietin-1/blood MH - Angiopoietin-2/*blood MH - Biomarkers/blood MH - Case-Control Studies MH - Chronic Disease MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Heart Failure/*blood/*physiopathology MH - *Hemodynamics MH - Humans MH - Italy MH - Male MH - Middle Aged MH - Natriuretic Peptide, Brain/blood MH - *Neovascularization, Physiologic MH - Oxygen Consumption MH - Peptide Fragments/blood MH - Receptor, TIE-2/blood MH - Regression Analysis MH - Ribonuclease, Pancreatic/blood MH - Severity of Illness Index MH - Stroke Volume MH - Up-Regulation MH - Vascular Endothelial Growth Factor A/blood MH - Ventricular Function, Left EDAT- 2011/04/01 06:00 MHDA- 2012/02/07 06:00 CRDT- 2011/04/01 06:00 PHST- 2011/04/01 06:00 [entrez] PHST- 2011/04/01 06:00 [pubmed] PHST- 2012/02/07 06:00 [medline] AID - 1741826710389410 [pii] AID - 10.1177/1741826710389410 [doi] PST - ppublish SO - Eur J Cardiovasc Prev Rehabil. 2011 Aug;18(4):607-14. doi: 10.1177/1741826710389410. Epub 2011 Feb 11.