Thromb Haemost 2003; 89(06): 990-995
DOI: 10.1055/s-0037-1613400
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers

Charalambos Antoniades
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Dimitris Tousoulis
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Costas Tentolouris
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Marina Toutouza
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Kyriakoula Marinou
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
George Goumas
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Costas Tsioufis
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Pavlos Toutouzas
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
,
Christodoulos Stefanadis
1   Cardiology Unit, Hippokration Hospital, Athens University Medical School, Athens, Greece
› Author Affiliations
Further Information

Publication History

Received 07 November 2002

Accepted after revision 11 March 2003

Publication Date:
08 December 2017 (online)

Summary

Smoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400IU/day (group B), vitamin C 2g/day plus vitamin E 800IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.

 
  • References

  • 1 Fuster U, Badimon L, Badimon J, Chesebro J. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242-50.
  • 2 Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, Deanfield JE. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993; 88: 2149-55.
  • 3 Morrow JD, Frei B, Longmire AW, Gaziano JM, Lynch SM, Shyr Y, Strauss WE, Oates JA, Roberts LJ. 2nd Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. N Engl J Med 1995; 332: 1198-203.
  • 4 Juhan-Vage I. Haemostatic parameters and vascular risk. Atherosclerosis 1996; 124: S49-55.
  • 5 Nielsen NE, Siegbahn A, Swahn E. Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics. J Intern Med 2000; 248: 151-8.
  • 6 Sakai H, Goto S, Kim JY, Aoki N, Abe S, Ichikawa N, Yoshida M, Nagaoka Y, Handa S. Plasma concentration of von Willebrand factor in acute myocardial infarction. Thromb Haemost 2000; 84: 204-9.
  • 7 Blann AD, McCollum CN. Von Willebrand factor and soluble thrombomodulin as predictors of adverse events among subjectswith peripheral or coronary atherosclerosis. Blood Coagul Fibrinolysis 1999; 10: 375-80.
  • 8 Blann AD, McCollum CN. Adverse influence of cigarette smoking on the endothelium. Thromb Haemost 1993; 70: 707-11.
  • 9 Scarabin PY, Aillaud MF, Amouyel P, Evans A, Luc G, Ferrieres J, Arveiler D, Juhan-Vague I. Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction-the PRIME study. Prospective Epidemiological Study of Myocardial Infarction. Thromb Haemost 1998; 80: 749-56.
  • 10 Hughes K, Choo M, Kuperan P, Ong CN, Aw TC. Cardiovascular risk factors in relation to cigarette smoking: a population-based survey among Asians in Singapore. Atherosclerosis 1998; 137: 253-8.
  • 11 Heitzer T, Just H, Münzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers. Circulation 1996; 94: 6-9.
  • 12 Motoyama T, Kawano H, Kugiyama K, Hirashima O, Ohgushi M, Yoshimura M, Ogawa H, Yasue H. Endothelium-dependent vasodilation in the brachial artery is impaired in smokers: effect of vitamin C. Am J Physiol 1997; 273: H1644-50.
  • 13 Raitakari OT, Adams MR, McCredie RJ, Griffiths KA, Stocker R, Celemajer DS. Oral vitamin C and endothelial function in smokers: Short-term improvement, but no sustained beneficial effect. J Am Coll Cardiol 2000; 35: 1616-21.
  • 14 Heitzer T, Yla Herttuala S, Wild E, Luoma J, Drexler H. Effect of vitamin E on endothelial vasodilator function in patients with hypercholesterolemia, chronic smoking or both. J Am Coll Cardiol 1999; 33: 499-505.
  • 15 Neunteufl T, Priglinger U, Heher S, Zehetgruber M, Soregi G, Lehr S, Huber K, Maurer G, Weidinger F, Kostner K. Effects of vitamin E on chronic and acute endothelial dysfunction in smokers. J Am Coll Cardiol 2000; 35: 277-83.
  • 16 Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of Antioxidant Vitamin Supplementation in 20 536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002; 360: 23-3325.
  • 17 Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 154-60.
  • 18 GISSI-Prevenzione Investigators Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E, after myocardial infarction: results of the GISSI-Prevenzione Trial. Lancet 1999; 354: 447-55.
  • 19 Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. Effect of the angiotensin-converting enzyme inhibitor imidapril on reactive hyperemia in patients with essential hypertension: relationship between treatment periods and resistance artery endothelial function. J Am Coll Cardiol 2001; 37: 863-70.
  • 20 Iwatsubo H, Nagano M, Sakai T, Kumamoto K, Morita R, Higaki J, Ogihara T, Hata T. Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. Hypertension 1997; 29: 286-90.
  • 21 Higashi Y, Sasaki S, Nakagawa K, Uwda T, Yoshimizu A, Kurisu S, Matsuura H. A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: A multi-center study. J Am Coll Cardiol 2000; 35: 284-91.
  • 22 Palace VP, Brown SB. HPLC determination of tocopherol, retinal, dehydroretinol and retinyl palmitate in tissues of laken char (salvelinus namaycush) exposed to coplanar 3,3’,4,4’,5-pentachlorobiphenyl. Environ Toxicol Chem 1994; 13: 473-6.
  • 23 Kishida E, Nishimoto Y, Kojo S. Secific determination of ascorbic acid with chemical derivatization and high-performance liquid chromatography. Anal Chem 64 1992; 1505-7.
  • 24 Nourooz-Zadeh J, Tajaddini-Sarmadi J, Wolff SP. Measurement of plasma hydroperoxide concentrations by the ferrous oxidation-xylenol orange assay in conjunction with triphenylphosphine. Anal Biochem 1994; 220: 403-9.
  • 25 Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 1991; 288: 481-7.
  • 26 Neuzil J, Thomas SR, Stocker R. Requirement for promotion, or inhibition by α-tocopherol of radical-induced initiation of plasma lipo-protein lipid peroxidattion. Free Radic Biol Med 1997; 22: 57-71.
  • 27 Vischer UM, Emeis JJ, Bilo HJ, Stehouwer CD, Thomsen C, Rasmussen O, Hermansen K, Wollheim CB, Ingerslev J. Von Willebrand factor (vWf) as a marker of endothelial activation in diabetes: improved reliability with parallel determination of the vWf propeptide (vWf:AgII). Thromb Haemost 1998; 80: 1002-7.
  • 28 Blann AD, Kirkpatrick U, Devine C, Naser S, McCollum CN. The influence of acute smoking on leucocytes, platelets and the endothelium. Atherosclerosis 1998; 141: 133-9.
  • 29 Abu-Zidan F, Farrant G, Zwi J, Simovic MO, Day T, Bonham MJD, Windsor JA. Plasma von Willebrand factor and intestinal ischemiareperfusion injury in rats. Thromb Res 1999; 94: 353-8.
  • 30 de Maat MP, Pijl H, Kluft C, Princen HM. Consumption of black and green tea had no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals. Eur J Clin Nutr 2000; 54: 757-63.
  • 31 Seljeflot I, Arnesen H, Brude IR, Nenseter MS, Drevon CA, Hjermann I. Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers. Eur J Clin Invest 1998; 28: 629-35.
  • 32 Nordt TK, Peter K, Ruef J, Kubler C. Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease. Thromb Haemost 1999; 82 (Suppl. 01) 14-8.
  • 33 Simpson AJ, Gray RS, Moore NR, Booth NA. The effects of chronic smoking on the fibrinolytic potential of plasma and platelets. Br J Haematol 1997; 97: 208-13.
  • 34 Thogersen AM, Jansson JH, Boman K, Nils-son TK, Weinehall L, Huhtasaari F, Hallmans G. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrin-olytic system as an independent primary risk factor. Circulation 1998; 98: 2241-7.
  • 35 Gris JC, Schved JF, Feugeas O, Aguilar-Martinez P, Arnaud A, Sanchez N, Sarlat C. Impact of smoking, physical training and weight reduction on fVII, PAI-1 and hemostatic markers in sedentary men. Thromb Haemost 1990; 64: 516-20.
  • 36 Ren S, Shen GX. Impact of antioxidants and HDL on glycated LDL-induced generation of fibrinolytic regulators from vascular endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 1688-93.
  • 37 Dimeny E, Fellstrom B. Metabolic abnormalities in renal transplant recipients. Risk factors and predictors of chronic graft dysfunction?. Nephrol Dial Transplant 1997; 12: 21-4.
  • 38 Bonfigli AR, Pieri C, Manfrini S, Testa I, Sirolla C, Ricciotti R, Marra M, Compagnucci P, Testa R. Vitamin E intake reduces plasmino-gen activator inhibitor type 1 in T2DM patients. Diabetes Nutr Metab 2001; 14: 71-7.
  • 39 Woodhouse PR, Meade TW, Khaw KT. Plasminogen activator inhibitor-1, the acute phase response and vitamin C. Atherosclerosis 1997; 133: 71-6.
  • 40 Orbe J, Rodriguez JA, Calvo A, Grau A, Belzunce MS, Martinez-Caro D, Paramo JA. Vitamins C and E attenuate plasminogen activator inhibitor-1 (PAI-1) expression in a hypercholesterolemic porcine model of angioplasty. Cardiovascular Res 2001; 49: 484-92.
  • 41 Hamsten A. The hemostatic system and coronary heart disease. Thromb Res 1993; 70: 1-38.
  • 42 Tofler GH, Stec JJ, Stubbe I, Beadle J, Feng D, Lipinska I, Taylor A. The effect of vitamin C supplementation on coagulability and lipid levels in healthy male subjects. Thromb Res 2000; 100: 35-41.
  • 43 Skrha J, Hodinar A, Kvasnicka J, Hilgertova J. Relationship of oxidative stress and fibrinbolysis in diabetes mellitus. Diabet Med 1996; 13: 800-5.