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Thromb Haemost 2002; 87(03): 415-420
DOI: 10.1055/s-0037-1613019
Review Article
Schattauer GmbH

Does Inflammatory Proteolytic Activity Contribute to the Increased Factor IX Activation Peptide in Men at High Risk of Coronary Heart Disease? A Preliminary Study

G. J. Miller
2   Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK
,
K. A. Bauer
1   Department of Medicine, V.A. Boston Health Care System and Beth Israel Deacones Medical Center, Harvard Medical School, Boston, Mass., USA
,
D. J. Howarth
2   Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK
,
J. P. Mitchell
2   Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK
,
J. A. Cooper
2   Medical Research Council Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, UK
› Author Affiliations
Further Information

Publication History

Received 20 August 2001

Accepted after resubmission 06 December 2001

Publication Date:
14 December 2017 (online)

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Summary

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.

Keywords

Coronary heart disease - factor IX - factor X - activation peptides - fibrinogen degradation product - inflammatory markers
 

  • References

  • 1 Morris JN. Recent history of coronary disease. Lancet 1951; i: 1-7 and 69–73.
    PubMedSearch in Google Scholar
  • 2 Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y, Thompson SG. Haemostatic function and cardiovascular death: early results of a prospective study. Lancet 1980; i: 1050-4.
    PubMedSearch in Google Scholar
  • 3 Poller L. Thrombosis and factor VII activity. J Clin Path 1957; 10: 348-50.
    CrossrefPubMedSearch in Google Scholar
  • 4 Wilhelmsen L, Svardsudd K, Koran-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-5.
    CrossrefPubMedSearch in Google Scholar
  • 5 De Wood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980; 303: 897-902.
    CrossrefPubMedSearch in Google Scholar
  • 6 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; ii: 533-7.
    PubMedSearch in Google Scholar
  • 7 Cooper JA, Miller GJ, Bauer KA, Morrissey JH, Meade TW, Howarth DJ, Barzegar S, Mitchell JP, Rosenberg RD. Comparison of novel haemostatic factors and conventional risk factors for prediction of coronary heart disease. Circulation 2000; 102: 2816-22.
    CrossrefPubMedSearch in Google Scholar
  • 8 Bauer KA, Kass BL, ten Cate H, Hawiger JJ, Rosenberg RD. Factor IX is activated in vivo by the tissue factor mechanism. Blood 1990; 76: 731-6.
    PubMedSearch in Google Scholar
  • 9 Stern D, Nawroth P, Handley D, Kisiel W. An endothelial cell-dependent pathway of coagulation. Proc Natl Acad Sci USA 1985; 82: 2523-7.
    CrossrefPubMedSearch in Google Scholar
  • 10 Jesty J, Spencer AK, Nemerson Y. The mechanism of activation of factor X. J Biol Chem 1974; 249: 5614-22.
    PubMedSearch in Google Scholar
  • 11 Bauer KA, Kass BL, ten Cate H, Bednarek MA, Hawiger JJ, Rosenberg RD. Detection of factor X activation in humans. Blood 1989; 74: 2007-15.
    PubMedSearch in Google Scholar
  • 12 Morrissey JH, Macik BG, Neuenschwander PF, Comp PC. Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 1993; 81: 734-44.
    PubMedSearch in Google Scholar
  • 13 Hoogendoorn H, Weitz JI, Giles AR. Evidence for the generation of elastase activity in a primate model of disseminated intravascular coagulation (DIC). Thromb Haemost 1993; 69: 1127 (Abstract).
    PubMedSearch in Google Scholar
  • 14 Dollery CM, McEwan JZR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77: 863-8.
    CrossrefPubMedSearch in Google Scholar
  • 15 Amaro A, Gude F, Gonzalez-Juanatey R, Iglesias C, Fernandez-Vasquez F, Garcia-Acuna J, Gil M. Plasma leukocyte elastase concentration in angiographically diagnosed coronary artery disease. Eur Heart J 1995; 16: 615-22.
    CrossrefPubMedSearch in Google Scholar
  • 16 Smedly LA, Tonnesen MG, Sandhaus RA, Haslett C, Guthrie LA, Johnston RB. Neutrophil-mediated injury to endothelial cells. Enhancement by endotoxin and essential role of neutrophil elastase. J Clin Invest 1986; 77: 1233-43.
    CrossrefPubMedSearch in Google Scholar
  • 17 Gillis S, Furie BC, Furie B. Interactions of neutrophils and coagulation proteins. Sem Hematol 1997; 34: 336-42.
    PubMedSearch in Google Scholar
  • 18 Samis JA, Kam E, Nesheim ME, Giles AR. Neutrophil elastase cleavage of human factor IX generates an activated factor IX-like product devoid of coagulant function. Blood 1998; 92: 1287-96.
    PubMedSearch in Google Scholar
  • 19 Anderssen T, Halvorsen H, Bajaj SP, Osterud B. Human leukocyte elastase and cathepsin G inactivate factor VII by limited proteolysis. Thromb Haemost 1993; 70: 414-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Allen DH, Tracy PB. Human coagulation factor V is activated to the functional cofactor by elastase and cathepsin G expressed at the monocyte surface. J Biol Chem 1995; 270: 1408-15.
    CrossrefPubMedSearch in Google Scholar
  • 21 Schmidt W, Egbring R, Havemann K. Effect of elastase-like and chymotrypsin-like neutral proteases from human granulocytes on isolated clotting factors. Thromb Res 1975; 06: 315-29.
    CrossrefPubMedSearch in Google Scholar
  • 22 Miller GJ, Bauer KA, Barzegar S, Cooper JA, Rosenberg RD. Increased activation of the haemostatic system in men at high risk for fatal coronary heart disease. Thromb Haemost 1996; 75: 767-71.
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Miller GJ, Bauer KA, Barzegar S, Foley AJ, Mitchell JP, Cooper JA. The effects of quality and timing of venepuncture on markers of blood coagulation in healthy middle-aged men. Thromb Haemost 1995; 73: 82-6.
    Thieme ConnectPubMedSearch in Google Scholar
  • 24 World Health Organization Regional Office for Europe. Myocardial infarction community registers. Public Health in Europe, no 5. Copenhagen: WHO, 1976
    PubMedSearch in Google Scholar
  • 25 Prineas RJ, Crow RS, Blackburn H. The Minnesota Code Manual of Electrocardiographic Findings. Standards and Procedures for Measurement and Classification. Boston: John Wright, PSC Inc; 1982
    Search in Google Scholar
  • 26 Von Clauss A. Gerrinungsphysiologische Schellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957; 77: 237-46.
    PubMedSearch in Google Scholar
  • 27 Bos R, van Leuven CJM, Stolk J, Hiemstra PS, Ronday HK, Nieuwenhuizen W. An enzyme immunoassay for polymorphonuclear leucocytemediated fibrinolysis. Europ J Clin Invest 1997; 27: 148-56.
    PubMedSearch in Google Scholar
  • 28 Sorensen JV, Jensen HP, Rahr HB, Borris LC, Lassen MR, Knudsen F. F1+2 and FpA in urine from patients with multiple trauma and healthy individuals. A pilot study. Thromb Res 1992; 67: 429-34.
    CrossrefPubMedSearch in Google Scholar
  • 29 Weinstein MJ, Chute LE, Schmitt GW, Hamburger RH, Bauer KA, Troll JH, Janson P, Deykin D. Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation. J Clin Invest 1985; 76: 1406-11.
    CrossrefPubMedSearch in Google Scholar
  • 30 Bajaj SP, Rapaport SI, Russell WA. Redetermination of the rate-limiting step in the activation of factor IX by factor XIa and by factor VIIa/tissue factor. Explanation for different electrophoretic radioactivity profiles obtained on activation of 3H-and 125I- labeled factor IX. Biochemistry 1983; 22: 4047-53.
    CrossrefPubMedSearch in Google Scholar
  • 31 Dinerman JL, Mehta JL, Saldeen TG, Emerson S, Wallin R, Davda R, Davidson A. Increased neutrophil elastase release in unstable angina pectoris and acute myocardial infarction. J Am Coll Cardiol 1990; 15: 1559-63.
    CrossrefPubMedSearch in Google Scholar
  • 32 Smith FB, Fowkes FGR, Rumley A, Lee AJ, Lowe GDO, Hau CM. Tissue plasminogen activator and leucocyte elastase as predictors of cardiovascular events in subjects with angina pectoris: Edinburgh Artery Study. Eur Heart J 2000; 21: 1607-13.
    CrossrefPubMedSearch in Google Scholar
  • 33 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340: 115-26.
    CrossrefPubMedSearch in Google Scholar
  • 34 Mantarri M, Tiula E, Alikoski T, Manninen V. Effects of hypertension and dyslipidemia on the decline in renal function. Hypertension 1995; 26: 670-5.
    CrossrefPubMedSearch in Google Scholar
  • 35 Piehlmeier W, Renner R, Schramm W, Kimmerling T, Garbe S, Proetzsch R, Fahn J, Piwernetz K, Landgraf R. Screening of diabetic patients for microalbuminuria in primary care – The PROSIT – Project. Exper Clin Endocrinol Diab 1999; 107: 244-51.
    PubMedSearch in Google Scholar
  • 36 Lee AJ, Lowe GDO, Woodward M, Tunstall-Pedoe H. Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease, and family history: the Scottish Heart Health Study. Br Heart J 1993; 69: 338-42.
    CrossrefPubMedSearch in Google Scholar
  • 37 Lee AJ, Smith WCS, Lowe GDO, Tunstall-Pedoe H. Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. J Clin Epidemiol 1990; 43: 913-9.
    CrossrefPubMedSearch in Google Scholar