The role of endostatin in coronary heart disease (CHD) is not well known. This study aimed to investigate the dynamics of endostatin, an antiangiogenic growth factor, within the coronary circulation and to elucidate its relation to coronary collateral formation in patients with CHD. We recruited 72 subjects with suspected or previously diagnosed CHD. Blood samples from the left ventricular (LV) cavity and coronary sinus (CS) were obtained during coronary angiography, and the serum concentration of endostatin was measured by enzyme-linked immunosorbent assay kits. Patients were then divided into 2 groups: the normal group (n = 15) defined as patients with atypical chest pain and no evidence of organic cardiac diseases and the CHD group (n = 57) defined as patients with >or=75% coronary stenosis at coronary angiography and chest pain on exertion. Endostatin in CS sera was significantly elevated in patients with CHD compared with normal subjects (median 79.7 [interquartile range 46.2 to 130.3] vs median 49.6 [interquartile range 29.1 to 84.5] ng/ml, p = 0.02). Spillover of endostatin (CS - LV value) from the coronary circulation in patients with CHD with severe stenosis was higher than in those with moderate stenosis (28.2 [4.8 to 48.6] vs 7.3 [-37.0 to 25.6] ng/ml, p = 0.01). In addition, endostatin production within the coronary circulation was higher in patients with poorly developed collaterals than in those with well-developed collaterals. In conclusion, endostatin is suggested to be produced from the coronary circulation in patients with CHD and may play an important role in the regulation of the growth of coronary collateral vessels.