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

被引:64
作者
Lapp, H
Boerrigter, G
Costello-Boerrigter, LC
Jaekel, K
Scheffold, T
Krakau, I
Schramm, M
Guelker, H
Stasch, JP
机构
[1] Herzzentrum Wuppertal, Med Klin 3, Helios Klinikum, D-42117 Wuppertal, Germany
[2] Univ Witten Herdecke, Inst Herz Kreislaufforsch, Witten, Germany
[3] Mayo Clin, Cardiorenal Res Lab, Rochester, MN USA
[4] Bayer AG, Inst Herz Kreislaufforsch, D-5600 Wuppertal, Germany
关键词
urotensin II; ischemic cardiomyopathy; heart failure; atherosclerosis;
D O I
10.1016/j.ijcard.2003.05.008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:93 / 97
页数:5
相关论文
共 20 条
[1]   No effect on central or peripheral blood pressure of systemic urotensin II infusion in humans [J].
Affolter, JT ;
Newby, DE ;
Wilkinson, IB ;
Winter, MJ ;
Balment, RJ ;
Webb, DJ .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2002, 54 (06) :617-621
[2]   Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14 [J].
Ames, RS ;
Sarau, HM ;
Chambers, JK ;
Willette, RN ;
Alyar, NV ;
Romanic, AM ;
Louden, CS ;
Foley, JJ ;
Sauermelch, CF ;
Coatney, RW ;
Ao, ZH ;
Disa, J ;
Holmes, SD ;
Stadel, JM ;
Martin, JD ;
Liu, WS ;
Glover, GI ;
Wilson, S ;
McNulty, DE ;
Ellis, CE ;
Elshourbagy, NA ;
Shabon, U ;
Trill, JJ ;
Hay, DWP ;
Ohlstein, EH ;
Bergsma, DJ ;
Douglas, SA .
NATURE, 1999, 401 (6750) :282-286
[3]   Urotensin II evokes potent vasoconstriction in humans in vivo [J].
Böhm, F ;
Pernow, J .
BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135 (01) :25-27
[4]   Natriuretic peptides in the pathophysiology of congestive heart failure [J].
Chen H.H. ;
Burnett Jr. J.C. .
Current Cardiology Reports, 2000, 2 (3) :198-205
[5]  
Clerico A, 2000, CLIN CHEM, V46, P1529
[6]   Cloning of the cDNA encoding the urotensin II precursor in frog and human reveals intense expression of the urotensin II gene in motoneurons of the spinal cord [J].
Coulouarn, Y ;
Lihrmann, I ;
Jegou, S ;
Anouar, Y ;
Tostivint, H ;
Beauvillain, JC ;
Conlon, JM ;
Bern, HA ;
Vaudry, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15803-15808
[7]   Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators [J].
Daggubati, S ;
Parks, JR ;
Overton, RM ;
Cintron, G ;
Schocken, DD ;
Vesely, DL .
CARDIOVASCULAR RESEARCH, 1997, 36 (02) :246-255
[8]   Congestive heart failure and expression of myocardial urotensin II [J].
Douglas, SA ;
Tayara, L ;
Ohlstein, EH ;
Halawa, N ;
Giaid, A .
LANCET, 2002, 359 (9322) :1990-1997
[9]   Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure [J].
Dschietzig, T ;
Bartsch, C ;
Pregla, R ;
Zurbrügg, HR ;
Armbruster, FP ;
Richter, C ;
Laule, M ;
Romeyke, E ;
Neubert, C ;
Voelter, W ;
Baumann, G ;
Stangl, K .
REGULATORY PEPTIDES, 2002, 110 (01) :33-38
[10]   Co-expression of urotensin II and its receptor (GPR14) in human cardiovascular and renal tissues [J].
Matsushita, M ;
Shichiri, M ;
Imai, T ;
Iwashina, M ;
Tanaka, H ;
Takasu, N ;
Hirata, Y .
JOURNAL OF HYPERTENSION, 2001, 19 (12) :2185-2190