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

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.

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.

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.

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.