Download PDF
Thromb Haemost 2007; 97(04): 642-649
DOI: 10.1160/TH06-08-0479
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Active endothelin is an important vasoconstrictor in acute coronary thrombi

Christopher Adlbrecht
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Diana Bonderman
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Christian Plass
2   2 Center of Physiology and Pathophysiology, and the Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria
,
Johannes Jakowitsch
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Gilbert Beran
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Wolfgang Sperker
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Peter Siostrzonek
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Dietmar Glogar
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Gerald Maurer
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
,
Irene M. Lang
1   Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology
› Author AffiliationsFinancial support: This research was supported by FWFS9406-B11 (to IML).
Further Information

Publication History

Received 30 August 2006

Accepted after resubmission 08 February 2007

Publication Date:
24 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Acute coronary syndrome is characterized by compromised blood flow at the epicardial and microvascular levels. We have previously shown that thrombectomy in ST-elevation myocardial infarction (STEMI) accelerates ST-segment resolution, possibly by preventing distal embolization. We hypothesized that thrombus constituents contribute to microcirculatory dysfunction. Therefore, we analyzed the molecular and cellular composition of acute coronary thrombi, and correlated vasoconstrictive mediators with the magnitude of ST-segment resolution within one hour of percutaneous coronary intervention (PCI). Fresh coronary thrombi were retrieved in 35 consecutive STEMI patients who were treated with the X-Sizer thrombectomy catheter, and thrombus cell counts and vasoconstrictor concentrations were assessed. Twelve-lead ECG recordings were analyzed prior to and one hour after PCI. Concentration of endothelin (ET) was 20.0 (7.9–52.2) fmol/ml in thrombus compared with 0.1 (0.1–0.3) fmol/ml in corresponding peripheral plasma (p<0.0001), representing a selective 280 (70.0–510.0)- fold enrichment, exceeding enrichment of noradrenaline, angiotensin II and serotonin. Human coronary thrombus homogenates exerted vasoconstriction of porcine coronary artery rings that was inhibited by the dual ET receptor blocker tezosentan. Extracted ET (r=0.523 p=0.026) and number of leukocytes (r=0.555 p=0.017) were correlated with the magnitude of STsegment resolution. In conclusion, the amount of active ET and white blood cells aspirated from STEMI target vessels correlated with improvement of territorial microcirculatory function as illustrated by enhanced ST-segment resolution.

Keywords

Acute myocardial infarction - thrombosis - endothelin / -receptors - leukocyte function / activation - arterial thrombosis
 

  • References

  • 1 Mizuno K, Satomura K, Miyamoto A. et al. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. N Engl J Med 1992; 326: 287-291.
    CrossrefPubMedSearch in Google Scholar
  • 2 Gibson CM, Cannon CP, Murphy S et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000; 101: 125-130.
    CrossrefPubMedSearch in Google Scholar
  • 3 Nunn CM, O'Neill WW, Rothbaum D. et al. Longterm outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial. J Am Coll Cardiol 1999; 33: 640-646.
    CrossrefPubMedSearch in Google Scholar
  • 4 The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. TIMI Study Group. N Engl J Med 1985; 312: 932-936.
    PubMedSearch in Google Scholar
  • 5 Abbo KM, Dooris M, Glazier S. et al. Features and outcome of no-reflow after percutaneous coronary intervention. Am J Cardiol 1995; 75: 778-782.
    CrossrefPubMedSearch in Google Scholar
  • 6 Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 2001; 22: 729-739.
    CrossrefPubMedSearch in Google Scholar
  • 7 Piana RN, Paik GY, Moscucci M. et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation 1994; 89: 2514-2518.
    CrossrefPubMedSearch in Google Scholar
  • 8 Wilson RF, Laxson DD, Lesser JR. et al. Intense microvascular constriction after angioplasty of acute thrombotic coronary arterial lesions. Lancet 1989; 1: 807-811.
    PubMedSearch in Google Scholar
  • 9 Mansaray M, Belcher PR, Vergroesen I. et al. Downstream resistance effects of intracoronary thrombosis in the stenosed canine coronary artery. Cardiovasc Res 1999; 42: 193-200.
    CrossrefPubMedSearch in Google Scholar
  • 10 Yanagisawa M, Kurihara H, Kimura S. et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332: 411-415.
    CrossrefPubMedSearch in Google Scholar
  • 11 Stone GW, Webb J, Cox DA. et al. Distal microcirculatory protection during percotaneous coronary intervention in acute ST-segment elevation myocardial infarction. J Am Med Assoc 2005; 293: 1063-1072.
    CrossrefPubMedSearch in Google Scholar
  • 12 Beran G, Lang I, Schreiber W. et al. Intracoronary thrombectomy with the X-sizer catheter system improves epicardial flow and accelerates ST-segment resolution in patients with acute coronary syndrome: a prospective, randomized, controlled study. Circulation 2002; 105: 2355-2360.
    CrossrefPubMedSearch in Google Scholar
  • 13 Mulvany MJ, Halpern W. Mechanical properties of vascular smooth muscle cells in situ. Nature 1976; 260: 617-619.
    CrossrefPubMedSearch in Google Scholar
  • 14 Clozel M, Ramuz H, Clozel JP. et al. Pharmacology of tezosentan, new endothelin receptor antagonist designed for parenteral use. J Pharmacol Exp Ther 1999; 290: 840-846.
    PubMedSearch in Google Scholar
  • 15 Bonderman D, Teml A, Jakowitsch J. et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99: 2794-2800.
    CrossrefPubMedSearch in Google Scholar
  • 16 De Luca G, Suryapranata H, Zijlstra F. et al. Symptom- onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty. J Am Coll Cardiol 2003; 42: 991-997.
    CrossrefPubMedSearch in Google Scholar
  • 17 Anderson RD, White HD, Ohman EM. et al. Predicting outcome after thrombolysis in acute myocardial infarction according to ST-segment resolution at 90 minutes: a substudy of the GUSTO-III trial. Global Use of Strategies To Open occluded coronary arteries. Am Heart J 2002; 144: 81-88.
    CrossrefPubMedSearch in Google Scholar
  • 18 Lefevre T, Garcia E, Reimers B. et al. X-sizer for thrombectomy in acute myocardial infarction improves ST-segment resolution: results of the X-sizer in AMI for negligible embolization and optimal ST resolution (X AMINE ST) trial. J Am Coll Cardiol 2005; 46: 246-252.
    CrossrefPubMedSearch in Google Scholar
  • 19 Levin ER. Endothelins. N Engl J Med 1995; 333: 356-363.
    CrossrefPubMedSearch in Google Scholar
  • 20 Bacon CR, Cary NR, Davenport AP. Endothelin peptide and receptors in human atherosclerotic coronary artery and aorta. Circ Res 1996; 79: 794-801.
    CrossrefPubMedSearch in Google Scholar
  • 21 Hasdai D, Holmes Jr. DR, Garratt KN. et al. Mechanical pressure and stretch release endothelin-1 from human atherosclerotic coronary arteries in vivo. Circulation 1997; 95: 357-362.
    CrossrefPubMedSearch in Google Scholar
  • 22 Nguyen QT, Cernacek P, Sirois MG. et al. Longterm effects of nonselective endothelin A and B receptor antagonism in postinfarction rat: importance of timing. Circulation 2001; 104: 2075-2081.
    CrossrefPubMedSearch in Google Scholar
  • 23 Clozel M, Qiu C, Qiu CS. et al. Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction. J Am Coll Cardiol 2002; 39: 142-147.
    PubMedSearch in Google Scholar
  • 24 Cambiaggi C, Mencarelli M, Muscettola M. et al. Gene expression of endothelin-1 (ET-1) and release of mature peptide by activated human neutrophils. Cytokine 2001; 14: 230-233.
    CrossrefPubMedSearch in Google Scholar
  • 25 Yamashita K, Discher DJ, Hu J. et al. Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein- 1, GATA-2, AND p300/CBP. J Biol Chem 2001; 276: 12645-12653.
    CrossrefPubMedSearch in Google Scholar
  • 26 Niccoli G, Lanza GA, Shaw S. et al. Endothelin-1 and acute myocardial infarction: a no-reflow mediator after successful percutaneous myocardial revascularization. Eur Heart J 2006; 27: 1793-1798.
    CrossrefPubMedSearch in Google Scholar
  • 27 Kurihara H, Yamaoki K, Nagai R. et al. Endothelin: a potent vasoconstrictor associated with coronary vasospasm. Life Sci 1989; 44: 1937-1943.
    CrossrefPubMedSearch in Google Scholar
  • 28 Adachi H, Shoji T, Goto K. Comparison of the effects of endothelin and Bay k 8644 on cardiohemodynamics in anesthetized pigs. Eur J Pharmacol 1991; 193: 57-65.
    CrossrefPubMedSearch in Google Scholar
  • 29 Halim A, Kanayama N, el Maradny E. et al. Coagulation in vivo microcirculation and in vitro caused by endothelin-1. Thromb Res 1993; 72: 203-209.
    CrossrefPubMedSearch in Google Scholar
  • 30 Pernow J, Kaijser L, Lundberg JM. et al. Comparable potent coronary constrictor effects of endothelin- 1 and big endothelin-1 in humans. Circulation 1996; 94: 2077-2082.
    CrossrefPubMedSearch in Google Scholar
  • 31 Molenaar P, O'Reilly G, Sharkey A. et al. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res 1993; 72: 526-538.
    CrossrefPubMedSearch in Google Scholar
  • 32 Lopez-Farre A, Caramelo C, Esteban A. et al. Effects of aspirin on platelet-neutrophil interactions. Role of nitric oxide and endothelin-1. Circulation 1995; 91: 2080-2088.
    CrossrefPubMedSearch in Google Scholar
  • 33 Naruko T, Ueda M, Haze K. et al. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation 2002; 106: 2894-2900.
    CrossrefPubMedSearch in Google Scholar
  • 34 Kirchhofer D, Riederer MA, Baumgartner HR. Specific accumulation of circulating monocytes and polymorphonuclear leukocytes on platelet thrombi in a vascular injury model. Blood 1997; 89: 1270-1278.
    PubMedSearch in Google Scholar
  • 35 Konstantopoulos K, Neelamegham S, Burns AR. et al. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and beta2-integrin. Circulation 1998; 98: 873-882.
    CrossrefPubMedSearch in Google Scholar
  • 36 Movat HZ, Wasi S. Severe microvascular injury induced by lysosomal releasates of human polymorphonuclear leukocytes. Increase in vasopermeability, hemorrhage, and microthrombosis due to degradation of subendothelial and perivascular matrices. Am J Pathol 1985; 121: 404-417.
    PubMedSearch in Google Scholar