Overexpression of Fibrinogen in ApoE*3-Leiden Transgenic Mice Does not Influence the Progression of Diet-Induced Atherosclerosis

F. Rezaee; M. J. Gijbels; E. H. Offerman; M. van der Linden; M. P. M. De Maat; J. H. Verheijen

doi:10.1055/s-0037-1613206

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(02): 329-334
DOI: 10.1055/s-0037-1613206

In Focus

Schattauer GmbH

Overexpression of Fibrinogen in ApoE*3-Leiden Transgenic Mice Does not Influence the Progression of Diet-Induced Atherosclerosis

F. Rezaee

¹Department of Vascular and Connective Tissue Research, Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

,

M. J. Gijbels

²Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

,

E. H. Offerman

¹Department of Vascular and Connective Tissue Research, Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

,

M. van der Linden

³Center for Human Drug Research (CHDR), Leiden, The Netherlands

,

M. P. M. De Maat

¹Department of Vascular and Connective Tissue Research, Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

,

J. H. Verheijen

¹Department of Vascular and Connective Tissue Research, Gaubius Laboratory, TNO-PG, Leiden, The Netherlands

› Author Affiliations

Abstract

Summary

Although many epidemiological studies have shown an association between hyperfibrinogenemia and atherosclerosis, it is not established whether elevated fibrinogen has an etiological role in the pathogenesis or is only a reflection of the ongoing disease.

We have studied the contribution of fibrinogen to the development of atherosclerosis in atherosclerosis-prone ApoE*3-Leiden mice that have been cross-bred with transgenic mice overexpressing fibrinogen. Genetic compound offspring were used to evaluate the progression of atherosclerotic lesions after being fed an atherogenic diet for 7 weeks. It was observed that the lesion area of the plaques as well as the severity of the lesions in the aortic valve was comparable in control single transgenic ApoE*3-Leiden mice and in double transgenic apoE*3-Leiden mice overexpressing fibrinogen. No thrombus or fibrin deposition was observed in atherosclerotic lesions in either group of mice.

These results indicate that elevated plasma fibrinogen concentrations in ApoE*3-Leiden transgenic mice do not affect the progression of diet-induced atherosclerotic lesions.

Keywords

Atherosclerosis - fibrinogen overexpression - transgenic mouse

Full Text

References

References
1 Ross R. The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993; 362: 801-9.
2 Ross R. Atherosclerosis – An inflammatory disease. N Engl J Med 1999; 116: 115-26.
3 Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310: 1137-40.
4 Ross R, Fuster V. The pathogenesis of atherosclerosis. In: Fuster V, Ross R, Topol EJ. editors. Atherosclerosis and coronary artery disease. Philadephia: Lippincott-Raven Publishers; 1996: 441-60.
5 Cortellaro M, Boschetti C, Cofrancesco E, Zanussi C, Catalano M, De Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tavazzi L, Tremoli E, Della AVolpe, Polli E. and PLAT Study Group, Progetto Lombardo Atero- Trombosi (PLAT) Study Group. The PLAT Study: hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients. Principal results. Arterioscler Thromb 1992; 12 (09) 1063-70.
6 Wilhelmsen L, Svardsudd K, Korsan-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.
7 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imenson JD, Mellows S, Miller GJ, North MRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-8.
8 Kannel WB, Wolf PA, Castelli WP, D’Agostino RBD. Fibrinogen and risk of cardiovascular disease. The Framingham Study. J Am Med Assoc 1987; 258: 1183-6.
9 Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a metaanalysis and review of the literature. Ann Intern Med 1993; 118: 956-63.
10 Heinrich J, Balleisen L, Schulte H, Assman G, van de Loo J. Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler Thromb 1994; 144: 54-9.
11 Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332: 635-41.
12 Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. J Am Med Assoc 1998; 279: 1477-82.
13 Smith EB. Fibrinogen, fibrin and fibrin degradation products in relation to atherosclerosis. Clin Haemat 1986; 15: 355-70.
14 Handa K, Kono S, Saku K, Sasaki J, Kawano T, Sasaki Y, Hiroki T. Plasma fibrinogen levels as an independent indicator of severity of coronary atherosclerosis. Atherosclerosis 1989; 77: 209-13.
15 Lassila R, Peltonen S, Lepantalo M, Saarinen O, Kauhanen P, Manninen V. Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin. Arterioscler Thromb 1993; 13: 1738-42.
16 Cremer P, Nagel D, Mann H, Labrot B, Muller-Berninger R, Elster H, Seidel D. Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study (GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 men. Atherosclerosis 1997; 129 (02) 221-30.
17 Folsom AR, Wu KK, Shahar E, Davis CE. Association of haemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. Arterioscler Thromb 1993; 13: 1829-36.
18 Kusher I. The phenomenon of acute phase response. Ann N Y Acad Sci 1982; 389: 39-48.
19 Koj A. in: The acute phase response to injury and infection. Gorden AH, Koj A. eds. Elsevier; Amsterdam: 1985. 10: 139-232.
20 Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91: 2488-96.
21 Sukovich DA, Kauser K, Shirly FD, Del vecchio V, Halks-Miller M, Rubanyi GM. Expression of interleukin-6 in atherosclerotic lesions of male ApoE-knockout mice inhibition by 17β-estradiol. Arterioscler Thromb Vasc Biol 1998; 18: 1498-505.
22 Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995; 91: 2844-50.
23 Ridker PM. Inflammation, infection, and cardiovascular disease: How good is the clinical evidence?. Circulation 1998; 98: 1671-4.
24 Gulledge AA, Rezaee F, Verheijen JH, Lord ST. A novel transgenic mouse model of hyperfibrinogenemia. Thromb Haemost 2001; 86 (02) 511-6.
25 van den Maagdenburg AMJM, Hofker MH, Krimpenfort PJA, de Bruin I, van Vlijmen B, van der Boom H, Havekes LM, Frants RR. Transgenic mice carrying the apolipoprotein E3-Leiden gene exhibit hyperlipoproteinemia. J Biol Chem 1993; 268: 10540-5.
26 Leppanen P, Luoma JS, Hofker MH, Havekes LM, Ylä HS. Characterization of atherosclerotic lesions in apoE3-Leiden transgenic mice. Atherosclerosis 1998; 136: 147-52.
27 Gijbels MJ, van der Cammen M, van der Laan LJ, Emeis JJ, Havekes LM, Hofker MH, Kraal G. Progression and regression of atherosclerosis in APOE3-Leiden transgenic mice. Atherosclerosis 1999; 143: 15-25.
28 Zhao SP, Smelt AH, Leuven JA, van den Maagdenberg AM, van den Laarse A, van ’t H. Lipoproteins in familial dysbetalipoproteinemia. Variation of serum cholesterol level associated with VLDL concentration. Arterioscler Thromb 1993; 13: 316-23.
29 van Vlijmen BJ, van den Maagdenberg MH, Gijbels MJ, van der Boom H, HogenEsch H, Frants RR, Hofker MH, Havekes LM. Diet-induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J Clin Invest 1994; 93: 1403-10.
30 Van Vlijmen BJ, Mensink RP, Offermans RF, Hofker MH, Havekes LM. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidaemic apolipoprotein E3-Leiden transgenic mice. J Lipid Res 1998; 39: 1181-8.
31 Groot PH, van Vlijmen BJ, Benson GM, Hofker MH, Schiffelers R, Vidgeon MHart, Havekes LM. Quantitative assessment of aortic atherosclerosis in APOE3-Leiden transgenic mice and its relationship to serum cholesterol exposure. Arterioscler Thromb Vasc Biol 1996; 16: 926-33.
32 Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 1987; 68 (03) 231-40.
33 Bradbury P, Rae K. Connective tissues and stains: in theory and practice of histological techniques. Bancroft JD, Stevens A. editors. Churchill Livingstone, Medical Division. London: Fourth edition. 1996: 113-38.
34 Koopman J, Maas A, Rezaee F, Havekes L, Verheijen JH, Gijbels M, Haverkate F. Fibrinogen and atherosclerosis: A study in transgenic mice. Fibrinol Proteol 1997; 11: 19-21.
35 Astrup T, Brakman P, Nissen U. The estimation of fibrinogen, a revision. Scand. J Clin Lab Invest 1965; 17: 57-65.
36 Rezaee F, Maas A, Verheijen JH, Koopman J. Effect of genetic background on plasma fibrinogen in mice. Possible relation with susceptibility for atherosclerosis. Atherosclerosis 2000; 151: 65.
37 Xiao Q, Danton MJ, Witte DP, Kowala MC, Valentine MT, Degen JL. Fibrinogen deficiency is compatible with the development of atherosclerosis in mice. J Clin Invest 1998; 101 (05) 1184-94.
38 Lord S, Gulledge A. Exploring a risk factor: diet-induced atherosclerosis in transgenic mice with elevated plasma fibrinogen. Thromb Haemost 1999; 1637: 521.
39 Schwartz CJ, Valente AJ, Kelly JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Rokitansky revisited. Semin Thromb Haemost 1988; 14: 189-95.
40 Bini A, Fenoglio JJJ, Mesa-tejada R, Kudryk B, Kaplan KL. Identification and distribution of fibrinogen, fibrin, and fibrin (ogen) degradation products in atherosclerosis: use of monoclonal antibodies. Arteriosclerosis 1989; 09: 109-21.
41 Bini A, Kudryk BJ. Fibrinogen in human atherosclerosis. Ann NY Acad Sci 1995; 748: 461-73.
42 Smith EB. Fibrin deposition and fibrin degradation products in atherosclerotic plaques. Thromb Res 1994; 75: 329-35.