Semin Vasc Med 2003; 03(4): 355-362
DOI: 10.1055/s-2004-815693
ETIOLOGY OF ACS

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Endothelial Dysfunction as a Predictor of Acute Coronary Syndromes

Krishna Kathir, Mark  R. Adams
  • Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
Further Information

Publication History

Publication Date:
03 February 2004 (online)

ABSTRACT

Endothelial dysfunction is a key early event in atherogenesis and is integral in the onset of acute coronary syndromes. Disruption of the normal endothelial functions leads to loss of vasomotor control, reduced production of nitric oxide, formation of a procoagulant surface, and promotion of inflammation. These events may lead to destabilization of atherosclerotic plaques and the onset of acute coronary syndromes. There are several direct and indirect ways of assessing endothelial dysfunction in vivo. Several of these measures of endothelial dysfunction have been shown to correlate with increased risk of adverse cardiovascular outcomes.

REFERENCES

  • 1 Palmer R M, Ashton D S, Moncada S. et al . Vascular endothelial cells synthesize nitric oxide from L-arginine.  Nature . 1988;  333 664-666
  • 2 Bassenge E, Heusch G. Endothelial and neuro-humoral control of coronary blood flow in health and disease.  Rev Physiol Biochem Pharmacol . 1990;  116 77-165
  • 3 Arnold W P, Mittal C K, Katsuki S. et al . Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations.  Proc Natl Acad Sci USA . 1977;  74 3203-3207
  • 4 Dinerman J L, Mehta J L. Endothelial, platelet and leukocyte interactions in ischemic heart disease: insights into potential mechanisms and their clinical relevance.  J Am Coll Cardiol . 1990;  16 207-222
  • 5 Boulanger C M, Luscher T F. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide.  J Clin Invest . 1990;  85 587-590
  • 6 De Caterina R, Libby P, Peng H-B. et al . Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.  J Clin Invest . 1995;  96 60-68
  • 7 Moncada S, Herman A G, Higgs E A. et al . Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium.  Thromb Res . 1977;  11 323-344
  • 8 Cody R J. The potential role of endothelin as a vasoconstrictor substance in congestive heart failure.  Eur Heart J . 1992;  13 1573-1578
  • 9 Rubanyi G M. The role of endothelium in cardiovascular homeostasis and diseases.  J Cardiovasc Pharmacol . 1993;  22 S1-S14
  • 10 Machovich R. Choices among the possible reaction routes catalyzed by thrombin.  Ann N Y Acad Sci . 1986;  485 170-183
  • 11 Stamler J S, Vaughan D E, Loscalzo J. et al . Synergistic disaggregation of platelets by tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin.  Circ Res . 1989;  65 796-804
  • 12 Vita J A, Treasure C B, Nabel E G. et al . Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.  Circulation . 1990;  81 491-497
  • 13 Celermajer D S, Sorensen K E, Gooch V M. et al . Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.  Lancet . 1992;  340 1111-1115
  • 14 Zeiher A M, Drexler H, Wollschager H. et al . Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis.  Circulation . 1991;  83 391-401
  • 15 Celermajer D S, Sorensen K E, Bull C. et al . Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction.  J Am Coll Cardiol . 1994;  24 1468-1474
  • 16 Freiman P C, Mitchell G G, Heistad D D. et al . Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates.  Circ Res . 1986;  58 783-789
  • 17 Ludmer P L, Selwyn A P, Shook T L. et al . Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.  N Engl J Med . 1986;  315 1046-1051
  • 18 Adams M R, Robinson J, McCredie R. et al . Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis.  J Am Coll Cardiol . 1998;  32 123-127
  • 19 Nabel E G, Selwyn A P, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis.  J Am Coll Cardiol . 1990;  16 349-356
  • 20 Gordon J B, Ganz P, Nabel E G. et al . Atherosclerosis influences the vasomotor response of epicardial coronary arteries to exercise.  J Clin Invest . 1989;  83 1946-1952
  • 21 Goldstein J L, Kita T, Brown M S. Defective lipoprotein receptors and atherosclerosis. Lessons from an animal counterpart of familial hypercholesterolemia.  N Engl J Med . 1983;  309 288-296
  • 22 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s.  Nature . 1993;  362 801-809
  • 23 Libby P. Molecular bases of the acute coronary syndromes.  Circulation . 1995;  91 2844-2850
  • 24 Fuster V, Badimon L, Badimon J J. et al . The pathogenesis of coronary artery disease and the acute coronary syndromes (2).  N Engl J Med . 1992;  326 310-318
  • 25 Arnman V, Nilsson A, Stemme S. et al . Expression of plasminogen activator inhibitor-1 mRNA in healthy, atherosclerotic and thrombotic human arteries and veins.  Thromb Res . 1994;  76 487-499
  • 26 Hamsten A. Hemostatic function and coronary artery disease.  N Engl J Med . 1995;  332 677-678
  • 27 Szczeklik A, Musial J, Undas A. et al . Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia.  Arterioscler Thromb Vasc Biol . 1996;  16 948-954
  • 28 Davi G, Ganci A, Averna M. et al . Thromboxane biosynthesis, neutrophil and coagulative activation in type IIa hypercholesterolemia.  Thromb Haemost . 1995;  74 1015-1019
  • 29 Jayakody L, Senaratne M, Thomson A. et al . Endothelium-dependent relaxation in experimental atherosclerosis in the rabbit.  Circ Res . 1987;  60 251-264
  • 30 Chappell S P, Lewis M J, Henderson A H. Effect of lipid feeding on endothelium dependent relaxation in rabbit aortic preparations.  Cardiovasc Res . 1987;  21 34-38
  • 31 Kugiyama K, Kerns S A, Morrisett J D. et al . Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.  Nature . 1990;  344 160-162
  • 32 Ohara Y, Peterson T E, Harrison D G. Hypercholesterolemia increases endothelial superoxide anion production.  J Clin Invest . 1993;  91 2546-2551
  • 33 Gryglewski R J, Palmer R M, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor.  Nature . 1986;  320 454-456
  • 34 Liao J K, Shin W S, Lee W Y. et al . Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.  J Biol Chem . 1995;  270 319-324
  • 35 Ohara Y, Sayegh H S, Yamin J J. et al . Regulation of endothelial constitutive nitric oxide synthase by protein kinase C.  Hypertension . 1995;  25 415-420
  • 36 Bode-Boger S M, Boger R H, Kienke S. et al . Elevated L-arginine/dimethylarginine ratio contributes to enhanced systemic NO production by dietary L-arginine in hypercholesterolemic rabbits.  Biochem Biophys Res Commun . 1996;  219 598-603
  • 37 Vallance P, Leone A, Calver A. et al . Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure.  Lancet . 1992;  339 572-575
  • 38 Joris I, Zand T, Nunnari J J. et al . Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats.  Am J Pathol . 1983;  113 341-358
  • 39 Mata P, Alonso R, Lopez-Farre A. et al . Effect of dietary fat saturation on LDL oxidation and monocyte adhesion to human endothelial cells in vitro.  Arterioscler Thromb Vasc Biol . 1996;  16 1347-1355
  • 40 Cybulsky M I, Gimbrone M A. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis.  Science . 1991;  251 788-791
  • 41 Kinlay S, Selwyn A P, Delagrange D. et al . Biological mechanisms for the clinical success of lipid-lowering in coronary artery disease and the use of surrogate end-points.  Curr Opin Lipidol . 1996;  7 389-397
  • 42 Xu X P, Meisel S R, Ong J M. et al . Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitor in human monocyte-derived macrophages.  Circulation . 1999;  99 993-998
  • 43 Radomski M W, Palmer R M, Moncada S. Comparative pharmacology of endothelium-derived relaxing factor, nitric oxide and prostacyclin in platelets.  Br J Pharmacol . 1987;  92 181-187
  • 44 Boulanger C M, Tanner F C, Bea M L. et al . Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium.  Circ Res . 1992;  70 1191-1197
  • 45 Arman V, Nilsson A, Stemme S. et al . Expression of plasminogen activator inhibitor-1 mRNA in healthy, atherosclerotic and thrombotic human arteries and veins.  Thromb Res . 1994;  76 487-499
  • 46 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes.  Circulation . 2001;  104 365-372
  • 47 Slowik M R, Min W, Ardito T. et al . Evidence that tumor necrosis factor triggers apoptosis in human endothelial cells by interleukin-1-converting enzyme-like protease-dependent and -independent pathways.  Lab Invest . 1997;  77 257-267
  • 48 Ohara Y, Peterson T E, Harrison D G. Hypercholesterolemia increases endothelial superoxide anion production.  J Clin Invest . 1993;  91 2546-2551
  • 49 Peng H B, Libby P, Liao J K. Induction and stabilization of I kappa B alpha by nitric oxide mediates inhibition of NF-kappa B.  J Biol Chem . 1995;  270 14214-14219
  • 50 Thurberg B, Collins T. The nuclear factor-kappa B/inhibitor of kappa B autoregulatory system and atherosclerosis.  Curr Opin Lipidol . 1998;  9 387-396
  • 51 Joannides R, Haefeli W E, Linder L. et al . Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.  Circulation . 1995;  91 1314-1319
  • 52 Drexler H, Zeiher A M. Progression of coronary endothelial dysfunction in man and its potential clinical significance.  Basic Res Cardiol . 1991;  86 (suppl 2) 223-232
  • 53 Creager M A, Cooke J P, Mendelsohn M E. et al . Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans.  J Clin Invest . 1990;  86 228-234
  • 54 Anderson T J, Uehata A, Gerhard M D. et al . Close relation of endothelial function in the human coronary and peripheral circulations.  J Am Coll Cardiol . 1995;  26 1235-1241
  • 55 Nobuyoshi M, Tanaka M, Nosaka H. et al . Progression of coronary atherosclerosis: is coronary spasm related to progression?.  J Am Coll Cardiol . 1991;  18 904-910
  • 56 Murakami T, Mizuno S, Kaku B. Clinical morbidities in subjects with Doppler-evaluated endothelial dysfunction of coronary artery.  J Am Coll Cardiol . 1998;  31 419A
  • 57 Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease.  Circulation . 2001;  104 2673-2678
  • 58 Suwaidi J A, Hamasaki S, Higano S T, Nishimura R N, Holmes Jr R D, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.  Circulation . 2000;  101 948-954
  • 59 Halcox J PJ, Schenke W H, Zalos G. et al . Prognostic value of coronary vascular endothelial dysfunction.  Circulation . 2002;  106 653-658
  • 60 Aikawa M, Sugiyama S, Hill C C. et al . Lipid lowering reduces oxidative stress and endothelial cell activation in rabbit atheroma.  Circulation . 2002;  106 1390-1396
  • 61 Bourcier T, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells.  Arterioscler Thromb Vasc Biol . 2000;  20 556-562
  • 62 Treasure C B, Klein J L, Weintraub W S. et al . Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary disease.  N Engl J Med . 1995;  332 481-487
  • 63 Marx N, Sukhova G K, Collins T. et al . PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells.  Circulation . 1999;  99 3125-3131
  • 64 Marx N, Mackman N, Schonbeck U. et al . PPARalpha activators inhibit tissue factor expression and activity in human monocytes.  Circulation . 2001;  103 213-219
  • 65 Neve B P, Corseaux D, Chinetti G. et al . PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages.  Circulation . 2001;  103 207-212
  • 66 Marx N, Sukhova G, Murphy C et al. Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator-activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro.  Am J Pathol . 1998;  153 17-23
  • 67 Staels B, Koenig W, Habib A. et al . Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators.  Nature . 1998;  393 790-793
  • 68 Marx N, Bourcier T, Sukhova G K. et al . PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease.  Arterioscler Thromb Vasc Biol . 1999;  19 546-551
    >