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CLINICAL RESEARCH: HEART FAILURE

Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure

^* Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, England,United Kingdom

Manuscript received June 25, 2003; revised manuscript received August 6, 2003, accepted August 18, 2003.

^* Reprint requests and correspondence: Prof. Gregory Y. H. Lip, Haemostasis Thrombolysis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England, United Kingdom.
g.y.h.lip{at}bham.ac.uk

OBJECTIVES: The goal of this research was to test the hypothesis that plasma angiopoietin (Ang-1), its soluble receptor tie-2, and Ang-2 levels would be abnormal in patients with acute and chronic congestive heart failure (CHF) when compared with healthy controls.

BACKGROUND: Increased plasma vascular endothelial growth factor (VEGF) in CHF is suggestive of excess angiogenesis—possibly driven by tissue hypoxia. However, other growth factors also have a major role in angiogenesis, such as those of the angiopoietin family (e.g., Ang-1, which exerts its activity via its receptor, tie-2, and Ang-2).

METHODS: We recruited 39 patients with acute CHF (mean age 67 ± 10 years), 40 patients with chronic CHF (mean age 63 ± 9 years), and 17 healthy controls (mean age 67 ± 7 years), all in sinus rhythm. Citrated plasma was analyzed for Ang-1, Ang-2, tie-2, and VEGF by enzyme-linked immunosorbent assay.

RESULTS: Angiopoietin-2 (p < 0.001), tie-2 (p < 0.05), and VEGF (p < 0.05) levels were all higher in acute CHF compared with controls. The Ang-2 levels were higher in acute CHF compared with chronic CHF (p < 0.001), but there were no significant differences in Ang-1 levels between the groups. The principal significant correlations were between Ang-2 and tie-2 (Spearman, r = 0.407; p < 0.0001) and between Ang-2 and ejection fraction (r = –0.241, p = 0.043). Although only marginally raised, levels of VEGF correlated with both Ang-2 (r = 0.468, p < 0.001) and tie-2 (r = 0.569, p < 0.001).

CONCLUSIONS: We have demonstrated abnormal levels of Ang-2 and tie-2, but normal Ang-1, in both CHF patients. These abnormalities may, alongside VEGF, indicate a role for these angiogenic factors in the pathophysiology of CHF.

Abbreviations and Acronyms   Ang = angiopoietin   CHF = congestive heart failure   CV = coefficient of variation   ELISA = enzyme-linked immunosorbent assay   HMG-CoA = hydroxymethylglutaryl-coenzyme A   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   RNA = ribonucleic acid   VEGF = vascular endothelial growth factor

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