The molecular basis and pathophysiology of pulmonary hypertension (PH) are rapidly evolving areas. Recently discovered angiopoietins (Ang) constitute a family of growth factors, and whether they play a causal or protective role in pulmonary hypertension has not been fully elucidated. Since left heart disease probably represents the most frequent cause of PH, we sought to determine whether there was a relationship between serum Ang-1 levels and pulmonary hypertension caused by mitral stenosis (MS). The study population was composed of 49 patients with isolated MS. These patients were then divided into group 1 [31 patients with severe MS: mitral valve area (MVA) <= 1.1 cm(2)] and group 2 (18 patients with mild-moderate MS: MVA 1.2-2.0 cm(2)). Twenty-one healthy volunteers comprised the control group (group 3). All of the subjects underwent complete transthoracic echocardiography with determination of systolic pulmonary artery pressure (PAPs). Ang-1 levels were determined in serum. Serum levels of Ang-1 were significantly higher in the control group compared to patients with severe (group 1) and mild-moderate (group 2) MS (p < 0.001). Ang-1 levels were found to have moderate inverse correlation with PAPs and left atrial (LA) diameter (r: -0.620, p < 0.001 and r: -0.489, p < 0.001, respectively). The AUC for the ROC curve for predicting PAPs < 50 mmHg by serum Ang-1 level was 0.824 (95% CI 0.722-0.926, p < 0.001). A serum level of Ang-1 above 34,656 pg/ml has 74% sensitivity and 80% specificity for predicting that PH is not severe (PAPs < 50 mmHg). In conclusion, the findings of this study are distinctive in the sense that they clearly demonstrate a negative correlation between serum Ang-1 levels and the degree of PH.