Angiopoietin-1, Angiopoietin-2 and Tie-2 in the Coronary Circulation of Patients With and Without Coronary Collateral Vessels

BACKGROUND: The role of the angiopoietin (Ang)/Tie-2 system in coronary collateral growth is not well understood, so the purpose of this study was to investigate and elucidate the relationship of this system to coronary collateral formation in patients with coronary artery disease (CAD). METHODS AND RESULTS: Fifty-nine patients with CAD were recruited. Blood samples from the left ventricle (LV) and coronary sinus (CS) were obtained during cardiac catheterization, and serum concentrations of Ang-1, Ang-2, and Tie-2 were measured by enzyme-linked immunosorbent assay. Patients were then classified as mild CAD (n=30), defined as </=90% stenosis of the coronary arterial luminal diameter, or severe CAD (n=29), which was total (or near total) coronary occlusion requiring coronary collateral growth. Ang-1, Ang-2, and Tie-2 in the LV and CS sera were not significantly different between groups. In the severe CAD group, spillover of Tie-2 (CS-LV value) from the coronary circulation was found in comparison with the mild CAD group (3.43+/-2.22 vs -3.29+/-1.54 ng/ml, p=0.01), whereas the CS-LV values of Ang-1 and Ang-2 did not differ between groups. Tie-2 production was markedly increased in patients with well-developed collaterals. A positive and significant correlation was found between coronary Ang-2 and Tie-2 levels (r=0.44, p<0.001). CONCLUSIONS: Tie-2 is probably produced in the coronary circulation and may induce the development or maintenance of coronary collaterals in CAD patients. Furthermore, the role of Ang-2 in the formation of coronary collaterals may be more important than that of Ang-1.