This Article Full Text Full Text (PDF) All Versions of this Article: 110/16/2355    most recent 01.CIR.0000138112.90641.7Fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, K. W. Articles by Blann, A. D. Search for Related Content PubMed PubMed Citation Articles by Lee, K. W. Articles by Blann, A. D. Pubmed/NCBI databases Substance via MeSH Related Collections Angiogenesis Pathophysiology Growth factors/cytokines Acute coronary syndromes Mechanism of atherosclerosis/growth factors Other Vascular biology

(Circulation. 2004;110:2355-2360.)
© 2004 American Heart Association, Inc.

Coronary Heart Disease

Plasma Angiopoietin-1, Angiopoietin-2, Angiopoietin Receptor Tie-2, and Vascular Endothelial Growth Factor Levels in Acute Coronary Syndromes

From the Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.

Correspondence to Professor G.Y.H. Lip, Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH UK. E-mail G.Y.H.LIP{at}bham.ac.uk

Received March 23, 2004; de novo received May 25, 2004; accepted June 21, 2004.

Background— Angiopoietin (Ang) -1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) regulate angiogenesis and may be important in myocardial collateral development. Elevated levels of growth factors and their receptors are reported in myocardial infarction (MI), but changes after an acute coronary event are unknown.

Methods and Results— Plasma Ang-1, Ang-2, Tie-2, and VEGF levels were measured on admission (baseline) and at 48 hours (acute stage) in 126 patients with acute coronary syndrome (82 MI, 44 unstable angina pectoris). Baseline levels were compared with those of 40 patients with stable angina and 40 healthy controls. Measurements were repeated in 38 MI patients at 6 and 18 weeks (chronic stage). Baseline Ang-2 and Tie-2 levels were highest in MI patients (P<0.001). Patients with MI and unstable angina pectoris had higher VEGF levels compared with stable angina patients and healthy control subjects (P<0.001). In patients with acute MI, serial changes in all indexes from baseline to 18 weeks were observed (all P<0.001). Ang-1 levels were unchanged from baseline to 6 weeks but were elevated at 18 weeks. Ang-2 changes followed a biphasic pattern, being higher at baseline and 6 weeks but lower at 48 hours and 18 weeks. Tie-2 levels increased from baseline and remained elevated in the chronic phase. VEGF peaked at 6 weeks and then decreased toward baseline at 18 weeks.

Conclusions— Plasma Ang-2, Tie-2, and VEGF levels but not Ang-1 levels were increased in patients with acute coronary syndrome. Serial changes in the plasma levels and interrelationships among Ang-1, Ang-2, Tie-2, and VEGF levels from the acute to the chronic stages in MI may reflect the progressive stages of angiogenesis activity in the ischemic-necrotic myocardium in vivo.

Key Words: acute coronary syndromes • angiogenesis • angiopoietins • vascular endothelial growth factor • receptor, Tie-2

This article has been cited by other articles:

				S-A Chang, H-J Kang, H-Y Lee, K-H Kim, J Hur, K-S Han, Y-B Park, and H-S Kim Peripheral blood stem cell mobilisation by granulocyte-colony stimulating factor in patients with acute and old myocardial infarction for intracoronary cell infusion Heart, August 15, 2009; 95(16): 1326 - 1330. [Abstract] [Full Text] [PDF]

				M. van Meurs, N. F. Kurniati, F. M. Wulfert, S. A. Asgeirsdottir, I. A. de Graaf, S. C. Satchell, P. W. Mathieson, R. M. Jongman, P. Kumpers, J. G. Zijlstra, et al. Shock-induced stress induces loss of microvascular endothelial Tie2 in the kidney which is not associated with reduced glomerular barrier function Am J Physiol Renal Physiol, August 1, 2009; 297(2): F272 - F281. [Abstract] [Full Text] [PDF]

				J.-X. Chen and A. Stinnett Disruption of Ang-1/Tie-2 Signaling Contributes to the Impaired Myocardial Vascular Maturation and Angiogenesis in Type II Diabetic Mice Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1606 - 1613. [Abstract] [Full Text] [PDF]

				C. M. Findley, R. G. Mitchell, B. D. Duscha, B. H. Annex, and C. D. Kontos Plasma Levels of Soluble Tie2 and Vascular Endothelial Growth Factor Distinguish Critical Limb Ischemia From Intermittent Claudication in Patients With Peripheral Arterial Disease J. Am. Coll. Cardiol., July 29, 2008; 52(5): 387 - 393. [Abstract] [Full Text] [PDF]

				Q.-h. Tuo, H. Zeng, A. Stinnett, H. Yu, J. L. Aschner, D.-F. Liao, and J.-X. Chen Critical role of angiopoietins/Tie-2 in hyperglycemic exacerbation of myocardial infarction and impaired angiogenesis Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2547 - H2557. [Abstract] [Full Text] [PDF]

				A. Tello-Montoliu, F. Marin, J. Patel, V. Roldan, L. Mainar, V. Vicente, F. Sogorb, and G. Y.H. Lip Plasma angiogenin levels in acute coronary syndromes: implications for prognosis Eur. Heart J., December 2, 2007; 28(24): 3006 - 3011. [Abstract] [Full Text] [PDF]

				C. M. Findley, M. J. Cudmore, A. Ahmed, and C. D. Kontos VEGF Induces Tie2 Shedding via a Phosphoinositide 3-Kinase/Akt Dependent Pathway to Modulate Tie2 Signaling Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2619 - 2626. [Abstract] [Full Text] [PDF]

				K. L. Kim, I.-S. Shin, J.-M. Kim, J.-H. Choi, J. Byun, E.-S. Jeon, W. Suh, and D.-K. Kim Interaction between Tie receptors modulates angiogenic activity of angiopoietin2 in endothelial progenitor cells Cardiovasc Res, December 1, 2006; 72(3): 394 - 402. [Abstract] [Full Text] [PDF]

				W. Bureau, P. Van Slyke, J. Jones, R. N. N. Han, N. L. Ward, D. J. Stewart, and D. J. Dumont Chronic systemic delivery of angiopoietin-2 reveals a possible independent angiogenic effect Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H948 - H956. [Abstract] [Full Text] [PDF]

				M. L. Lindsey, G. P. Escobar, L. W. Dobrucki, D. K. Goshorn, S. Bouges, J. T. Mingoia, D. M. McClister Jr., H. Su, J. Gannon, C. MacGillivray, et al. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H232 - H239. [Abstract] [Full Text] [PDF]

				D. Wolf, H. Rumpold, E. Gunsilius, W. Wojakowski, M. Tendera, K. Maslankiewicz, R. Wyderka, A. Ochala, A. Michalowska, M. Majka, et al. Response Circulation, May 24, 2005; 111(20): e307 - e308. [Full Text] [PDF]