Skip to main content

Advertisement

SpringerLink
Log in

Urotensin-II and cardiovascular diseases

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Urotensin-II (U-II) is a vasoactive factor with pleiotropic effects. U-II exerts its activity by binding to a G-protein-coupled receptor termed UT. U-II and its receptor are highly expressed in the cardiovascular system. Increased U-II plasma levels have been reported in patients with cardiovascular disease of varying etiologies. We and others have shown that U-II and UT expression is elevated in both clinical and experimental heart failure and atherosclerosis. U-II induces cardiac fibrosis by increasing fibroblast collagen synthesis. In addition, U-II induces cardiomyocyte hypertrophy and increased vascular smooth muscle cell proliferation. We have shown that U-II antagonism using a selective U-II blocker, SB-611812, attenuates cardiac dysfunction by decreasing cardiomyocyte hypertrophy and cardiac fibrosis. We have also shown that SB-611812 reduces neointimal thickening and increases lumen diameter in a rat restenosis model of carotid artery angioplasty. These findings suggest an important role for U-II in cardiovascular dysfunction and remodeling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Douglas SA, Tayara L, Ohlstein EH, et al.: Congestive heart failure and expression of myocardial urotensin II. Lancet 2002, 359:1990–1997.

    Article  PubMed  CAS  Google Scholar 

  2. Ng LL, Loke I, O’Brien RJ, et al.: Plasma urotensin in human systolic heart failure. Circulation 2002, 106:2877–2880.

    Article  PubMed  CAS  Google Scholar 

  3. Richards AM, Nicholls MG, Lainchbury JG, et al.: Plasma urotensin II in heart failure. Lancet 2002, 360:545–546.

    Article  PubMed  CAS  Google Scholar 

  4. Russell FD, Meyers D, Galbraith AJ, et al.: Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure. Am J Physiol Heart Circ Physiol 2003, 285:H1576-H1581.

    PubMed  CAS  Google Scholar 

  5. Lapp H, Boerrigter G, Costello-Boerrigter LC, et al.: Elevated plasma human urotensin-II-like immunoreactivity in ischemic cardiomyopathy. Int J Cardiol 2004, 94:93–97.

    Article  PubMed  Google Scholar 

  6. Gruson D, Rousseau MF, Ahn SA, et al.: Circulating urotensin II levels in moderate to severe congestive heart failure: its relations with myocardial function and well established neurohormonal markers. Peptides 2006, 27:1527–1531.

    Article  PubMed  CAS  Google Scholar 

  7. Simpson CM, Penny DJ, Stocker CF, Shekerdemian LS: Urotensin II is elevated in children with congenital heart disease. Heart 2006, 92:983–984.

    Article  PubMed  CAS  Google Scholar 

  8. Dschietzig T, Bartsch C, Pregla R, et al.: Plasma levels and cardiovascular gene expression of urotensin-II in human heart failure. Regul Pept 2002, 110:33–38.

    Article  PubMed  CAS  Google Scholar 

  9. Kruger S, Graf J, Kunz D, et al.: Urotensin II in patients with chronic heart failure. Eur J Heart Fail 2005, 7:475–478.

    Article  PubMed  CAS  Google Scholar 

  10. Joyal D, Huynh T, Aiyar N, et al.: Urotensin-II levels in acute coronary syndromes. Int J Cardiol 2006, 108:31–35.

    Article  PubMed  Google Scholar 

  11. Zoccali C, Mallamaci F, Tripepi G, et al.: Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal disease. Kidney Int 2006, 69:1253–1258.

    Article  PubMed  CAS  Google Scholar 

  12. Lim M, Honisett S, Sparkes CD, et al.: Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure. Circulation 2004, 109:1212–1214. This study demonstrates the pathophysiologic relevance of increased U-II levels in patients with chronic heart failure by demonstrating U-II-induced vasodilatation in normal controls and paradoxic vasoconstriction in the patients.

    Article  PubMed  CAS  Google Scholar 

  13. Tzanidis A, Hannan RD, Thomas WG, et al.: Direct actions of urotensin II on the heart: implications for cardiac fibrosis and hypertrophy. Circ Res 2003, 93:246–253.

    Article  PubMed  CAS  Google Scholar 

  14. Johns DG, Ao Z, Naselsky D, et al.: Urotensin-II-mediated cardiomyocyte hypertrophy: effect of receptor antagonism and role of inflammatory mediators. Naunyn Schmiedebergs Arch Pharmacol 2004, 370:238–250.

    Article  PubMed  CAS  Google Scholar 

  15. Kompa AR, Thomas WG, See F, et al.: Cardiovascular role of urotensin II: effect of chronic infusion in the rat. Peptides 2004, 25:1783–1788.

    Article  PubMed  CAS  Google Scholar 

  16. Wang H, Mehta JL, Chen K, et al.: Human urotensin II modulates collagen synthesis and the expression of MMP-1 in human endothelial cells. J Cardiovasc Pharmacol 2004, 44:577–581.

    Article  PubMed  Google Scholar 

  17. Bousette N, Hu F, Ohlstein EH, et al.: Urotensin-II blockade with SB-611812 attenuates cardiac dysfunction in a rat model of coronary artery ligation. J Mol Cell Cardiol 2006, 41:285–295. This is the first study to demonstrate a therapeutic effect of U-II antagonism, including attenuated diastolic dysfunction and a reduction in myocardial hypertrophy, in a model of congestive heart failure.

    Article  PubMed  CAS  Google Scholar 

  18. Bousette N, Pottinger J, Ramli W, et al.: Urotensin-II receptor blockade with SB-611812 attenuates cardiac remodeling in experimental ischemic heart disease. Peptides 2006, In press.

  19. Nishikawa N, Masuyama T, Yamamoto K, et al.: Long-term administration of amlodipine prevents decompensation to diastolic heart failure in hypertensive rats. J Am Coll Cardiol 2001, 38:1539–1545.

    Article  PubMed  CAS  Google Scholar 

  20. Cheung BM, Leung R, Man YB, Wong LY: Plasma concentration of urotensin II is raised in hypertension. J Hypertens 2004, 22:1341–1344.

    Article  PubMed  CAS  Google Scholar 

  21. Rdzanek A, Filipiak KJ, Karpinski G, et al.: Exercise urotensin II dynamics in myocardial infarction survivors with and without hypertension. Int J Cardiol 2006, 110:175–178.

    Article  PubMed  Google Scholar 

  22. Thompson JP, Watt P, Sanghavi S, et al.: A comparison of cerebrospinal fiuid and plasma urotensin II concentrations in normotensive and hypertensive patients undergoing urological surgery during spinal anesthesia: a pilot study. Anesth Analg 2003, 97:1501–1503.

    Article  PubMed  CAS  Google Scholar 

  23. Balat O, Aksoy F, Kutlar I, et al.: Increased plasma levels of urotensin-II in preeclampsia-eclampsia: a new mediator in pathogenesis? Eur J Obstet Gynecol Reprod Biol 2005, 120:33–38.

    Article  PubMed  CAS  Google Scholar 

  24. Cowley E, Thompson JP, Sharpe P, et al.: Effects of preeclampsia on maternal plasma, cerebrospinal fiuid, and umbilical cord urotensin II concentrations: a pilot study. Br J Anaesth 2005, 95:495–499.

    Article  PubMed  CAS  Google Scholar 

  25. Sondermeijer B, Kompa A, Komesaroff P, Krum H: Effect of exogenous urotensin-II on vascular tone in skin microcirculation of patients with essential hypertension. Am J Hypertens 2005, 18(9 Pt 1):1195–1199.

    Article  PubMed  CAS  Google Scholar 

  26. Qi J, Du J, Tang X, et al.: The upregulation of endothelial nitric oxide synthase and urotensin-II is associated with pulmonary hypertension and vascular diseases in rats produced by aortocaval shunting. Heart Vessels 2004, 19:81–88.

    Article  PubMed  Google Scholar 

  27. Djordjevic T, BelAiba RS, Bonello S, et al.: Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells. Arterioscler Thromb Vasc Biol 2005, 25:519–525.

    Article  PubMed  CAS  Google Scholar 

  28. Bousette N, Patel L, Douglas SA, et al.: Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta. Atherosclerosis 2004, 176:117–123.

    Article  PubMed  CAS  Google Scholar 

  29. Hassan GS, Douglas SA, Ohlstein EH, Giaid A: Expression of urotensin-II in human coronary atherosclerosis. Peptides 2005, 26:2464–2472.

    Article  PubMed  CAS  Google Scholar 

  30. Maguire JJ, Kuc RE, Wiley KE, et al.: Cellular distribution of immunoreactive urotensin-II in human tissues with evidence of increased expression in atherosclerosis and a greater constrictor response of small compared to large coronary arteries. Peptides 2004, 25:1767–1774.

    Article  PubMed  CAS  Google Scholar 

  31. Heringlake M, Kox T, Uzun O, et al.: The relationship between urotensin II plasma immunoreactivity and left ventricular filling pressures in coronary artery disease. Regul Pept 2004, 121:129–136.

    Article  PubMed  CAS  Google Scholar 

  32. Wang ZJ, Shi LB, Xiong ZW, et al.: Alteration of vascular urotensin II receptor in mice with apolipoprotein E gene knockout. Peptides 2006, 27:858–863.

    Article  PubMed  CAS  Google Scholar 

  33. Salonen R, Salonen JT: Determinants of carotid intimamedia thickness: a population-based ultrasonography study in eastern Finnish men. J Intern Med 1991, 229:225–231.

    Article  PubMed  CAS  Google Scholar 

  34. Sauzeau V, Le Mellionnec E, Bertoglio J, et al.: Human urotensin II-induced contraction and arterial smooth muscle cell proliferation are mediated by RhoA and Rho-kinase. Circ Res 2001, 88:1102–1104.

    PubMed  CAS  Google Scholar 

  35. Watanabe T, Pakala R, Katagiri T, Benedict CR: Synergistic effect of urotensin II with serotonin on vascular smooth muscle cell proliferation. J Hypertens 2001, 19:2191–2196.

    Article  PubMed  CAS  Google Scholar 

  36. Watanabe T, Koba S, Katagiri T, et al.: Lysophosphatidylcholine potentiates the mitogenic effect of various vasoactive compounds on rabbit aortic smooth muscle cells. Jpn Heart J 2002, 43:409–416.

    Article  PubMed  CAS  Google Scholar 

  37. Rakowski E, Hassan GS, Dhanak D, et al.: A role for urotensin II in restenosis following balloon angioplasty: use of a selective UT receptor blocker. J Mol Cell Cardiol 2005, 39:785–791.

    Article  PubMed  CAS  Google Scholar 

  38. Watanabe T, Suguro T, Kanome T, et al.: Human urotensin II accelerates foam cell formation in human monocytederived macrophages. Hypertension 2005, 46:738–744.

    Article  PubMed  CAS  Google Scholar 

  39. Roberts WC: Preventing and arresting coronary atherosclerosis. Am Heart J 1995, 130(3 Pt 1):580–600.

    Article  PubMed  CAS  Google Scholar 

  40. Sheridan MA, Bern HA: Both somatostatin and the caudal neuropeptide, urotensin II, stimulate lipid mobilization from coho salmon liver incubated in vitro. Regul Pept 1986, 14:333–344.

    Article  PubMed  CAS  Google Scholar 

  41. Gendron G, Simard B, Gobeil F Jr, et al.: Human urotensin-II enhances plasma extravasation in specific vascular districts in Wistar rats. Can J Physiol Pharmacol 2004, 82:16–21.

    Article  PubMed  CAS  Google Scholar 

  42. Vergura R, Camarda V, Rizzi A, et al.: Urotensin II stimulates plasma extravasation in mice via UT receptor activation. Naunyn Schmiedebergs Arch Pharmacol 2004, 370:347–352.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Montreal General Hospital, Suite L3-109, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada

    Adel Giaid PhD

Authors
  1. Nicolas Bousette MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adel Giaid PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adel Giaid PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bousette, N., Giaid, A. Urotensin-II and cardiovascular diseases. Current Science Inc 8, 479–483 (2006). https://doi.org/10.1007/s11906-006-0026-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-006-0026-7

Keywords

Search

Navigation