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Vitamin C pp 59–71Cite as

Vitamin C and Cardiovascular Disease: Mechanisms of Action

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Abstract

Atherosclerosis and its clinical manifestations, particularly angina pectoris, myocardial infarction and ischemic stroke, is the single most important cause of morbidity and mortality in the Western world [1]. The initial stage of atherosclerotic lesion development is characterized by the local accumulation of low-density lipoprotein (LDL) and the recruitment of monocytes to the arterial wall [2, 3]. Once in the arterial wall, the monocytes differentiate into resident macrophages and then gradually may be converted to lipid-laden foam cells. Foam cells are the hallmark of the earliest atherosclerotic lesion called the “fatty streak.”

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References

  1. Gotto AJ, Farmer JA (1988) Risk factors for coronary artery disease. In: Braunwald E (ed) Heart disease: a textbook of cardiovascular medicine, 3rd edn. Saunders, Philadelphia, pp 1153–1190

    Google Scholar 

  2. Schwartz CJ, Valente AJ (1994) The pathogenesis of atherosclerosis. In: Frei B (ed) Natural antioxidants in human health and disease. Academic, San Diego, pp 287–302

    Google Scholar 

  3. Cybulsky MI, Gimbrone MA Jr (1991) Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251:788–791

    Article  PubMed  CAS  Google Scholar 

  4. Henriksen T, Mahoney EM, Steinberg D (1981) Enhanced macrophage degradation of low density lipoprotein previously incubated with cultured endothelial cells: recognition by receptor for acetylated low density lipoproteins. Proc Natl Acad Sci USA 78:6499–6503

    Article  PubMed  CAS  Google Scholar 

  5. Heinecke JW, Baker L, Rosen H, Chait A (1986) Superoxide-mediated modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Invest 77:757–761

    Article  PubMed  CAS  Google Scholar 

  6. Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963–20966

    Article  PubMed  CAS  Google Scholar 

  7. Berliner JA, Territo MC, Sevanian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM (1990) Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Invest 85:1260–1266

    Article  PubMed  CAS  Google Scholar 

  8. Frostegard J, Haegerstrand A, Giglund M, Nilsson J (1991) Biologically modified LDL increases the adhesive properties of endothelial cells. Atherosclerosis 90:119–126

    Article  PubMed  CAS  Google Scholar 

  9. Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ (1990) Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature 344:254–257

    Article  PubMed  CAS  Google Scholar 

  10. Quinn MT, Parthasarathy S, Fong LG, Steinberg D (1987) Oxidatively modified low density lipoproteins: a potential role in recruitment and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 84:2995–2998

    Article  PubMed  CAS  Google Scholar 

  11. Krieger M, Herz J (1994) Structures and functions of multiligand lipoprotein receptors: macrophage scavenger receptors and LDL receptor-related protein (LRP). Ann Rev Biochem 63:601–637

    Google Scholar 

  12. Heery JM, Kozak M, Stafforini DM, Jones DA, Zimmerman GA, Mclntyre TM, Prescott SM (1995) Oxidatively modified LDL contains phospholipids with platelet-activating factor-like activity and stimulates the growth of smooth muscle cells. J Clin Invest 96:2322–2230

    Article  PubMed  CAS  Google Scholar 

  13. Simon BC, Cunningham LD, Cohen RA (1990) Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery. J Clin Invest 86:75–79

    Article  PubMed  CAS  Google Scholar 

  14. Chin JH, Azhar S, Hoffman BB (1992) Inactivation of endothelial derived relaxing factor by oxidized lipoproteins. J Clin Invest 89:10–18

    Article  PubMed  CAS  Google Scholar 

  15. Esterbauer H, Jürgens G, Quehenberger O, Koller E (1987) Autoxidation of human low density lipoprotein: loss of polyunsaturated fatty acids and vitamin E and generation of aldehydes. J Lipid Res 28:495–509

    CAS  Google Scholar 

  16. Haberland ME, Olch CL, Fogelman AM (1984) Role of lysines in mediating interaction of modified low density lipoproteins with the scavenger receptor of human monocyte macrophages. J Biol Chem 259:11305–11311

    PubMed  CAS  Google Scholar 

  17. Bowry VW, Stocker R (1993) Tocopherol-mediated peroxidation. The prooxidant effect of vitamin E on the radical-initiated oxidation of human low-density lipoprotein. J Am Chem Soc 115:6029–6044

    Article  CAS  Google Scholar 

  18. Bowry VW, Mohr D, Cleary J, Stocker R (1995) Prevention of tocopherol-mediated peroxidation in ubiquinol-10-free human low density lipoprotein. J Biol Chem 270:5756–5763.

    Article  PubMed  CAS  Google Scholar 

  19. Steinbrecher UP, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81:3883–3887

    Article  PubMed  CAS  Google Scholar 

  20. Ehrenwald E, Chisolm GM, Fox PL (1994) Intact human ceruloplasmin oxidatively modifies low density lipoprotein. J Clin Invest 93:1493–1501

    Article  PubMed  CAS  Google Scholar 

  21. Hazell LJ, van den Berg JJ, Stocker R (1994) Oxidation of low-density lipoprotein by hypochlorite causes aggregation that is mediated by modification of lysine residues rather than lipid oxidation. Biochem J 302:297–304

    PubMed  CAS  Google Scholar 

  22. Savenkova MI, Mueller DM, Heinecke JW (1994) Tyrosyl radical generated by myeloperoxidase is a physiological catalyst for the initiation of lipid peroxidation in low density lipoprotein. J Biol Chem 269:20394–20400

    PubMed  CAS  Google Scholar 

  23. Moore KP, Darley-Usmar V, Morrow J, Roberts LJ II (1995) Formation of F2-iso-prostanes during oxidation of human low-density lipoprotein and plasma by per-oxynitrite. Circ Res 77:335–341

    PubMed  CAS  Google Scholar 

  24. Lynch SM, Frei B (1994) Antioxidants as antiatherogens: animal studies. In: Frei B (ed) Natural antioxidants in human health and disease. Academic, San Diego, pp 353–385

    Google Scholar 

  25. Diaz MN, Frei B, Vita JA, Keaney JF Jr (1997) Antioxidants and atherosclerotic heart disease. N Engl J Med 337:408–416

    Article  PubMed  CAS  Google Scholar 

  26. Fruebis J, Carew TE, Palinski W (1995) Effect of vitamin E on atherogenesis in LDL receptor-deficient rabbits. Atherosclerosis 117:217–224

    Article  PubMed  CAS  Google Scholar 

  27. Shaish A, Daugherty A, O’Sullivan F, Schonfeld G, Heinecke JW (1995) Beta-carotene inhibits atherosclerosis in hypercholesterolemic rabbits. J Clin Invest 96:2075–2082

    Article  PubMed  CAS  Google Scholar 

  28. Losonczy KG, Harris TB, Havlik RJ (1996) Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr 64:190–196

    PubMed  CAS  Google Scholar 

  29. Nyyssonen K, Parviainen MT, Salonen R, Tuomilehto J, Salonen JT (1997) Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. Br Med J 314:634–638

    Article  CAS  Google Scholar 

  30. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 330:1029–1035

    Article  Google Scholar 

  31. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, Belanger C, LaMotte F (1996) Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334:1145–1149

    Article  PubMed  CAS  Google Scholar 

  32. Kritchevsky SB, Shimakawa T, Tell GS, Dennis B, Carpenter M, Eckfeldt JH, Peacher-Ryan H, Heiss G (1995) Dietary antioxidants and carotid artery wall thickness. The ARIC Study. Circulation 92:2142–2150

    CAS  Google Scholar 

  33. Gale CR, Martyn CN, Winter PD, Cooper C (1995) Vitamin C and risk of death from stroke and coronary heart disease in a cohort of elderly people. Br Med J 310:1563–1566

    Article  CAS  Google Scholar 

  34. Frei B, Stocker R, Ames BN (1988) Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci USA 85:9748–9752

    Article  PubMed  CAS  Google Scholar 

  35. Frei B, England L, Ames BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86:6377–6381

    Article  PubMed  CAS  Google Scholar 

  36. Frei B, Forte T, Ames BN, Cross CE (1991) Gas-phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma: protective effects of ascorbate. Biochem J 277:133–138

    PubMed  CAS  Google Scholar 

  37. Jialal I, Vega GL, Grundy SM (1990) Physiologic levels of ascorbate inhibit oxidative modification of low density lipoprotein. Atherosclerosis 82:185–191

    Article  PubMed  CAS  Google Scholar 

  38. Stocker R, Bowry VW, Frei B (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci USA 88:1646–1650

    Article  PubMed  CAS  Google Scholar 

  39. Retsky KL, Freeman MW, Frei B (1993) Ascorbate oxidation product(s) protect human low density lipoprotein against atherogenic modification. Anti- rather than pro-oxidant activity of vitamin C in the presence of transition metal ions. J Biol Chem 268:1304–1309

    PubMed  CAS  Google Scholar 

  40. Stait SE, Leake DS (1994) Ascorbate can either increase or decrease low density lipoprotein modification. FEBS Lett 341:263–267

    Article  PubMed  CAS  Google Scholar 

  41. Retsky KL, Frei B (1995) Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low density lipoprotein. Biochim Biophys Acta 1257: 279–287

    PubMed  Google Scholar 

  42. Hatta A, Frei B (1995) Oxidative modification and antioxidant protection of human low density lipoprotein at high and low oxygen partial pressures. J Lipid Res 36:2383–2393

    PubMed  CAS  Google Scholar 

  43. Martin A, Frei B (1997) Both intracellular and extracellular vitamin C inhibit atherogenic modification of LDL by human vascular endothelial cells. Arterioscler Thromb Vasc Biol 17:1583–1590

    Article  PubMed  CAS  Google Scholar 

  44. Sato K, Niki E, Shimasaki H (1990) Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and C. Arch Biochem Biophys 279:402–405

    Article  CAS  Google Scholar 

  45. Neuzil J, Thomas SR, Stocker R (1997) Requirement for, promotion, or inhibition by

    Google Scholar 

  46. alpha-tocopherol of radical-induced initiation of plasma lipoprotein lipid peroxidation. Free Rad Biol Med 22:57–71

    Google Scholar 

  47. Uchida K, Kawakishi S (1990) Site-specific oxidation of angiotensin I by copper[II] and L-ascorbate: Conversion of histidine residues to 2-imidazolones. Arch Biochem Biophys 283:20–26

    Article  PubMed  CAS  Google Scholar 

  48. Kuzuya M, Yamada K, Hayashi T, Funaki C, Naito M, Asai K, Kuzuya F (1992) Role of lipoprotein-copper complex in copper catalyzed-peroxidation of low-density lipoprotein. Biochim Biophys Acta 1123:334–341

    PubMed  CAS  Google Scholar 

  49. Harats D, Ben-Nairn M, Dabach Y, Hollander G, Havivi E, Stein O, Stein Y (1990) Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 85:47–54

    Article  PubMed  CAS  Google Scholar 

  50. Reaven PD, Khouw A, Beltz WF, Parthasarathy S, Witztum JL (1993) Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not beta-carotene. Arterioscler Thromb 13:590–600

    Google Scholar 

  51. Fuller CJ, Grundy SM, Norkus EP, Jialal I (1996) Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 119:139–150

    Article  PubMed  CAS  Google Scholar 

  52. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA (1996) Ascorbate reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 93:1107–1113

    PubMed  CAS  Google Scholar 

  53. Ting HH, Timimi FK, Boles KS, Creager SJ, Ganz P, Creager MA (1996) Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 97:22–28

    Article  PubMed  CAS  Google Scholar 

  54. Heitzer T, Just H, Munzel T (1996) Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 94:6–9

    PubMed  CAS  Google Scholar 

  55. Ting HH, Timimi FK, Haley EA, Roddy MA, Ganz P, Creager MA (1997) Vitamin C improves endothelium-dependent vasodilation in forearm resistance vessels of humans with hypercholesterolemia. Circulation 95:2617–2622

    PubMed  CAS  Google Scholar 

  56. Solzbach U, Hornig B, Jeserich M, Just H (1997) Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 96:1513–1519

    PubMed  CAS  Google Scholar 

  57. Gryglewski RJ, Palmer RM, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320:454–456

    Article  PubMed  CAS  Google Scholar 

  58. Meister A (1994) Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 269: 9397–9400

    PubMed  CAS  Google Scholar 

  59. Vita JA, Frei B, Holbrook M, Gokce N, Leaf C, Keaney JF Jr (1998) Endothelial function in patients with coronary artery disease is sensitive to intracellular redox status (submitted for publication)

    Google Scholar 

  60. Lehr HA, Frei B, Arfors KE (1994) Vitamin C prevents cigarette smoke-induced leukocyte aggregation and adhesion to endothelium in vivo. Proc Natl Acad Sci USA 91:7688–7692

    Article  PubMed  CAS  Google Scholar 

  61. Lehr HA, Frei B, Olofsson M, Carew TE, Arfors KE (1995) Protection from oxidized LDL-induced leukocyte adhesion to micro- and macrovascular endothelium in vivo by vitamin C but not by vitamin E. Circulation 91:1525–1532

    PubMed  CAS  Google Scholar 

  62. Weber C, Erl W, Weber K, Weber PC (1996) Increased adhesiveness of isolated monocytes to endothelium is prevented by vitamin C intake in smokers. Circulation 93:1488–1492

    PubMed  CAS  Google Scholar 

  63. Adams MR, Jessup W, Celermajer DS (1997) Cigarette smoking is associated with increased human monocyte adhesion to endothelial cells: reversibility with oral L-arginine but not vitamin C. J Am Coll Cardiol 29:491–497

    Article  PubMed  CAS  Google Scholar 

  64. Simon JA (1992) Vitamin C and cardiovascular disease: a review. J Am Coll Nutr 11:107–125

    PubMed  CAS  Google Scholar 

  65. Hallfrisch J, Singh VN, Muller DC, Baldwin H, Bannon ME, Andres R (1994) High plasma vitamin C associated with high plasma HDL- and HDL2 cholesterol. Am J Clin Nutr 60:100–105

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA

    B. Frei

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  1. B. Frei
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Editor information

Editors and Affiliations

  1. Institute of Pharmacological Sciences, Faculty of Pharmacy, University of Milan, Italy

    Rodolfo Paoletti

  2. Institute of Physiological Chemistry, University of Düsseldorf, Germany

    Helmut Sies

  3. Merck Pharma, Self-Medication International, Merck KGaA, Darmstadt, Germany

    Joachim Bug

  4. Ethical Drugs Medical Department, Bracco Spa, Milan, Italy

    Enzo Grossi

  5. Nutrition Foundation of Italy, Milano, Italy

    Andrea Poli

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© 1998 Springer-Verlag Italia, Milano

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Frei, B. (1998). Vitamin C and Cardiovascular Disease: Mechanisms of Action. In: Paoletti, R., Sies, H., Bug, J., Grossi, E., Poli, A. (eds) Vitamin C. Springer, Milano. https://doi.org/10.1007/978-88-470-2244-7_7

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  • DOI: https://doi.org/10.1007/978-88-470-2244-7_7

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-0027-8

  • Online ISBN: 978-88-470-2244-7

  • eBook Packages: Springer Book Archive

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