Elevated plasma human urotensin-II-like immunoreactivity in ischemic cardiomyopathy

Background: The recently discovered, vasoactive, cyclic undecapeptide human urotensin-II (hU-II), and its G-protein coupled receptor (GPR14) are both expressed in the human cardiovascular system. Little is known about the pathophysiological relevance of hU-II. We hypothesised that circulating hU-II is elevated in patients with coronary artery disease (CAD) corresponding to the degree of cardiac dysfunction. Methods: 38 patients were diagnosed with coronary artery disease by left heart catheterization, and their functional status was classified according to the New York Heart Association (NYHA). hU-II-like immunoreactivity (hU-II-LI) was measured using a novel specific and sensitive enzyme-linked immunoassay. Calculations were performed with log-transformed hU-II-LI values. Results: hU-II-LI correlated positively with left ventricular end diastolic pressure (LVEDP) (r = 0.32, P = 0.05) and tended to correlate inversely with left ventricular ejection fraction (LV-EF) (r = -0.31, P = 0.061). There was a positive correlation between hU-II-LI and NYHA class (r = 0.53, P = 0.001). Circulating hU-II-LI was significantly higher in patients with NYHA class III (4822 +/- 723 pg/ml, N = 13) than in patients with class I (1884 +/- 642 pg/ml, N = 9, P = 0.007) or class II (2294 +/- 426 pg/ml, N = 15, P = 0.046). There was no difference between classes I and II (P = 0.83). Furthermore, hU-II-LI correlated significantly with B-type natriuretic peptide, a marker for heart failure (r = 0.40, P = 0.025). In a linear regression analysis, NYHA class was the only significant independent predictor of hU-II-LI. Conclusions: The present study demonstrates that plasma hU-II-LI rises significantly in proportion to parameters of cardiac dysfunction and functional impairment in patients with coronary artery disease. These results suggest a pathophysiological role for hU-II in cardiac disease and warrant further investigation. (C) 2003 Elsevier Ireland Ltd. All rights reserved.