Advertisement

Hypercholesterolaemia and Vascular Function

  • G. K. Goode
  • A. M. Heagerty
Part of the Experimental Biology and Medicine book series (EBAM, volume 26)

Abstract

Hypercholesterolaemia is a major risk factor for coronary heart disease and is associated with atheroma formation1, which tends to affect large and medium sized arteries especially at sites of turbulent blood flow. An important event in this process is an alteration in the functional or structural properties of the vascular endothelium. Evidence suggests that this endothelial dysfunction is an early event in atherogenesis and may well precede the development of atherosclerosis2,3. Studies in cholesterol-fed animals4–7 and humans with raised serum lipids8–10 have demonstrated abnormalities in vascular function which is usually manifested by an impairment in endothelium-dependent vasorelaxation, although altered smooth muscle sensitivity9 or poteniated vasoconstriction11 have also been suggested. We shall discuss the evidence that raised serum lipids affects arterial function, with particular attention to their effects on small arteries.

Keywords

Endothelial Dysfunction Rabbit Aorta Calcium Ionophore A23187 Porcine Coronary Artery Arterial Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Gordon T, Kannel W.B, Castelli WB, Dawber T.R Lipoproteins, cardiovascular disease and death. The Framingham study. Arch Intern Med. 141: 1128–1131, 1981.PubMedCrossRefGoogle Scholar
  2. 2.
    Healy B. Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. J Am Coll Cardiol. 16: 357–359, 1990.PubMedCrossRefGoogle Scholar
  3. 3.
    Celennajer 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. 340: 1111–1115, 1992.CrossRefGoogle Scholar
  4. 4.
    Verbeuren T.J, Jordaens F.H, Zonnekeyn LL, Van Hove C.E, Coene M-C, Herman A.G. Effect of hypercholesterolaemia on vascular reactivity in the rabbit. Endothelium-dependent and endothelium-independent contractions and relaxations in isolated arteries of control and hypercholesterolaemic rabbits. Circ Res 58: 552–564, 1986.PubMedCrossRefGoogle Scholar
  5. 5.
    Freiman P.C, Mitchell G.G, Heistad D.D, Armstrong M.L, Harrison D.G. Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates. Circ Res 58: 783–789, 1986.PubMedCrossRefGoogle Scholar
  6. 6.
    Shimokawa H, Van Houtte P.M. Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolaemia and atherosclerosis. Circ Res 64: 900–914, 1989.PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen RA, Zitnay KM, Haudenchild C.C, Cunningham L.D. Loss of selective endothelial cell vasoactive functions caused by hypercholesterolaemia in pig coronary arteries. Circ Res 63: 903–910, 1988.PubMedCrossRefGoogle Scholar
  8. 8.
    Bossaller C,Habib G.B, Yamamoto H, Williams C, Wells S, Henry P.D. Impaired muscarinic endothelium-dependent relaxation and cyclic 5’-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 79: 170–174, 1987.Google Scholar
  9. 9.
    Creager M.A, Cooke,LP, Mendlesohn M.E, Gallagher S.J, Coleman S.M, Loscalzo J, Dzau V.J Impaired vasodilation of forearm resistance vessels in hypercholesterolaemic humans. J Clin Invest 86: 228–234, 1990.Google Scholar
  10. 10.
    Zeiher A.M, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 83: 391–401, 1991.PubMedCrossRefGoogle Scholar
  11. 11.
    Heistad D.D, Annstrong M.L, Marcus M.L, Piegors D..1; Mark A.L. Augmented responses to vasoconstrictor stimuli in hypercholesterolaemic and atherosclerotic monkeys. Circ Res. 54: 711–718, 1984.PubMedCrossRefGoogle Scholar
  12. 12.
    Yamamoto H, Bossaller C, Cartwright J, Henry P.P. Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit. J Clin Invest 81: 1752–1758, 1988.PubMedCrossRefGoogle Scholar
  13. 13.
    Kuo L, Davis M.J, Cannon M.S, Chilian W.M. Pathophysiological Consequences of Atherosclerosis Extend into the Coronary Microcirculation. Circ Res 70: 465–476, 1992.PubMedCrossRefGoogle Scholar
  14. 14.
    Selke F.W, Armstrong M.L, Harrison D.G. Endothelium-Dependent Vascular Relaxation is Abnormal in the Coronary Microcirculation of Atherosclerotic Primates Circulation. 81: 1586–1593, 1990.Google Scholar
  15. 15.
    Goode G.K, Heagerty A.M. Small Artery Endothelial function is restored by Cholesterol Reduction in Human Subjects. J Vasc Res 31 (S1): 14, 1994.Google Scholar
  16. 16.
    Mulvany M.J, Halpem W. Contractile Properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rat. Circ Res 41: 19–26, 197. 7.Google Scholar
  17. 17.
    Minor R.L, Myers P.R, Gueira R, Bates J.N, Harrison D.G. Diet induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta. J Clin Invest 86: 2109 2116, 1990.Google Scholar
  18. 18.
    Martin W, Viliani G.M, Jothianandan D, Furchgott R.F. Selective blockage of endothelium-dependent and glyceryl trinitate-induced relaxation by haemoglobin and methylene blue in the rabbit aorta. J Pharmacol Exp Ther 232: 708716, 1985.Google Scholar
  19. 19.
    Cooke J.P, Andon N.A, Girerd X.J, Hirsh A.T, Creager M.A. Arginine restores cholinergic relaxation of hypecholesterolaemic rabbit thoracic aorta. Circulation 83: 1057–1062, 1991.PubMedCrossRefGoogle Scholar
  20. 20.
    Just H. Correction of endothelial dysfunction in the coronary microcirulation of hypercholesterolaemic patients by L-Arginine. LancetGoogle Scholar
  21. 21.
    Creager M.A, Gallager S.J, Girerd X.J, Colman S.M, Dzau V.J, Cooke J.P. L-Arginine improves Endothelium-Dependent Vasodilation in Hypercholesterolaemic Humans. J Clin Invest 90: 1248–1253, 1992.PubMedCrossRefGoogle Scholar
  22. 22.
    Minor RI, Myers P.R, Gyerra R, Bates 1N, Hanison D.G. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta J.Clin Invest 86: 2109 2116, 1990.Google Scholar
  23. 23.
    Ohara Y, Peterson T.E, Harrison D.G. Hypercholesterolaemia increases endothelial superoxide anion production. J Clin Invest 91: 2546–2551, 1993.PubMedCrossRefGoogle Scholar
  24. 24.
    Jacobs M, Plane F, Bnickdoifer KR Native and oxidised low density lipoproteins have different inhibitory effects on endothium-derived relaxing factor in the rabbit aorta. Br J Pharmacol 100: 21–26, 1990.Google Scholar
  25. 25.
    Simon B.C, Cunningham LD, Cohen R.P. Oxidised low density lipoproteins cause contraction and inhibit endothelium dependent relaxation in the pig coronary artery. J Clin Invest 86: 75–79, 1990.PubMedCrossRefGoogle Scholar
  26. 26.
    Stewart D.J, Monge JC. Hyperlipidaemia and endothelial dysfunction. Current opinion in Lipidology. 4: 319–324, 1993.CrossRefGoogle Scholar
  27. 27.
    Shimokawa H, Flavahan N.A, VanHoutte P.M. Loss of endothelial pertussintoxin-sensitive G-protein function in atherosclerotic porcine coronary arteries. Circulation 83: 652–660, 1991.PubMedCrossRefGoogle Scholar
  28. 28.
    Flavahan N.A. Atherosclerosis or Lipoprotein-induced Endothelial Dysfunction. Circulation 85: 1927–1938, 1992.PubMedCrossRefGoogle Scholar
  29. 29.
    Hanison D.G, Armstrong M.L, Freimann P.C, Heistad D.D. Restoration of endothelium-dependent relaxation by dietary treatment of atherosclerosis. J Clin Invest 80: 1808–1811, 1987.CrossRefGoogle Scholar
  30. 30.
    Osborne J A, Lento P.H, Siefried M.R, Stahl G.L, Fusman B, Lefer A.M. Cardiovascular effects of acute hypercholesterolaemia in rabbits: reversal with Lovastatin treatment. J Clin Invest 83: 465–473, 1989.Google Scholar
  31. 31.
    Leung W.H, Lau C-P, Wong C-K Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolaemic patients. Lancet 341: 1496–1500, 1993.PubMedCrossRefGoogle Scholar
  32. 32.
    Belcher 1D, Balla J, Balla G, Jacobs D.R, Gross M, Jacob H.S, Vencellotti G.M. Vitamin E, LDL and Endothelium. Arterioscler Thromb 13: 1779–1789, 1993.Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • G. K. Goode
    • 1
  • A. M. Heagerty
    • 1
  1. 1.Department of MedicineUniversity Hospital of South ManchesterManchesterUK

Personalised recommendations