Gender differences in the expression of erythrocyte aggregation in relation to Bβ-fibrinogen gene polymorphisms in apparently healthy individuals

Einor Ben Assayag; Irena Bova; Shlomo Berliner; Hava Peretz; Sali Usher; Itzhak Shapira; Natan M. Bornstein

doi:10.1160/TH05-08-0578

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(03): 428-433
DOI: 10.1160/TH05-08-0578

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Gender differences in the expression of erythrocyte aggregation in relation to Bβ-fibrinogen gene polymorphisms in apparently healthy individuals

Einor Ben Assayag

¹Department of Neurology, Tel Aviv University, Tel Aviv, Israel

,

Irena Bova

¹Department of Neurology, Tel Aviv University, Tel Aviv, Israel

,

Shlomo Berliner

²Department of Medicine “D”, Tel Aviv University, Tel Aviv, Israel

,

Hava Peretz

³Laboratory of Clinical Biochemistry, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

Sali Usher

³Laboratory of Clinical Biochemistry, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

Itzhak Shapira

²Department of Medicine “D”, Tel Aviv University, Tel Aviv, Israel

,

Natan M. Bornstein

¹Department of Neurology, Tel Aviv University, Tel Aviv, Israel

› Author Affiliations

Abstract

Summary

An increased erythrocyte aggregation (EA) is associated with capillary slow flow, tissue hypoxemia and endothelial dysfunction. Fibrinogen is a major determinant in the formation of aggregated red blood cells. It has been suggested that the Bβ-fibrinogen –455G/A polymorphism is associated with erythrocyte hyperaggregability in men with coronary artery disease.The purpose of this study was to investigate the influence of the β-fibrinogen –455G/A polymorphism on erythrocyte aggregation in apparently healthy individuals. Plasma fibrinogen, red blood cell count, serum lipids, erythrocyte sedimentation rate, and the genotype of the Bβ-fibrinogen –455G/A polymorphism were examined in a cohort of 545 apparently healthy individuals and those with atherothrombotic risk factors. A whole blood erythrocyte aggregation test was performed by using a simple slide test and image analysis. In men, EA levels and plasma fibrinogen levels were significantly higher in subjects carrying the –455A allele compared to subjects with the –455 GG genotype.This association did not exist in women carrying the fibrinogen –455A allele.The –455GA/AA men presented significantly higher correlation between the plasma fibrinogen concentrations and EA. This observation raises the prospect of possible change in the functional properties of the –455GA/AA fibrinogen, enhancing its ability to induce EH. This study suggests that the Bβ-fibrinogen –455A allele is related to EH in men only. Putative mechanism could be hyperfibrinogenemia anda functional change in the fibrinogen molecule that alters its ability to interact with red blood cells and supports the aggregability of these cells.

Keywords

Erythrocyte aggregation - fibrinogen - gene polymorphism

Full Text

References

References
1 Soutani M. et al. Quantitative evaluation of flow dynamics of erythrocytes in microvessels: influence of erythrocyte aggregation. Am J Physiol 1995; 268: H1959-H1965.
2 Schmid-Schonbein H. Blood rheology and physiology of microcirculation. Ric Clin Lab 1981; 11 (Suppl. 01) 13-33.
3 Bishop JJ. et al. Effect of erythrocyte aggregation on velocity profiles in venules. Am J Physiol Heart Circ Physiol 2001; 280: H222-H236.
4 Mchedlishvili G. et al. Microcirculatory stasis induced by hemorheological disorders: further evidence. Microcirculation 1999; 06: 97-106.
5 Cabel M. et al. Contribution of red blood cell aggregation to venous vascular resistance in skeletal muscle. Am J Physiol 1997; 272: H1020-H1032.
6 Fisher M, Meiselman HJ. Hemorheological factors in cerebral ischemia. Stroke 1991; 22: 1164-9.
7 Mchedlishvili G. et al. Local RBC aggregation disturbing blood fluidity and causing stasis in microvessels. Clin Hemorheol Microcirc 2002; 26: 99-106.
8 Bishop JJ. et al. Relationship between erythrocyte aggregate size and flow rate in skeletal muscle venules. Am J Physiol Heart Circ Physiol 2004; 286: H113-H120.
9 Yalcin O. et al. Graded alterations of RBC aggregation influence in vivo blood flow resistance. Am J Physiol Heart Circ Physiol 2004; 287: H2644-H2650.
10 Kim S. et al. Aggregate formation of erythrocytes in postcapillary venules. Am J Physiol Heart Circ Physiol 2005; 288: H584-H590.
11 Tateishi N. et al. O2 release from erythrocytes flowing ina narrow O2-permeable tube: effects of erythrocyte aggregation. Am J Physiol Heart Circ Physiol 2001; 281: H448-H456.
12 Tateishi N. et al. Reduced oxygen release from erythrocytes by the acceleration-induced flow shift, observed in an oxygen-permeable narrow tube. J Biomech 2002; 35: 1241-51.
13 Baskurt OK. et al. Modulation of endothelial nitric oxide synthase expression by red blood cell aggregation. Am J Physiol Heart Circ Physiol 2004; 286: H222-H229.
14 Weng X. et al. Contribution of acute-phase proteins and cardiovascular risk factors to erythrocyte aggregation in normolipidemic and hyperlipidemic individuals. Thromb Haemost 1998; 80: 903-8.
15 Weng X. et al. Contribution of the -455G/A polymorphism at the β-fibrinogen gene to erythrocyte aggregation in patients with coronary artery disease. Thromb Haemost 1999; 82: 1406-11.
16 Talstad I. et al. Influence of plasma proteins on erythrocyte morphology and sedimentation. Scand J Haematol 1983; 31: 478-84.
17 Rampling MW. et al. The effects of fibrinogen and its plasmin degradation products on the rheology of erythrocyte suspensions. Clin Hemorheol 1984; 04: 533-43.
18 Fabry TL. Mechanism of erythrocyte aggregation and sedimentation. Blood 1987; 70: 1572-6.
19 Schechner V. et al. Significant dominance of fibrinogen over immunoglobulins, C-reactive protein, cholesterol and triglycerides in maintaining increased red blood cell adhesiveness/aggregation in the peripheral venous blood: a model in hypercholesterolaemic patients. Eur J Clin Invest 2003; 33: 955-61.
20 Demiroglu H. The importance of erythrocyte aggregation in blood rheology: considerations of the pathophysiology of thrombotic disorders. Blood 1997; 89: 4236.
21 Demiroglu H. et al. Erythrocyte aggregability in patients with coronary heart disease. Clin Hemorheol 1996; 16: 313-7.
22 Mchedlishvili G. et al. Comparative values of erythrocyte aggregability versus other indices of hemorheological disorders in patients with ischemic brain infarcts. Clin Hemorheol Microcirc 2000; 22: 9-15.
23 Kwaan HC. et al. Digital ischemia and gangrene due to red blood cell aggregation induced by acquired dysfibrinogenemia. J Vasc Surg 1997; 26: 1061-8.
24 Koscielny J. et al. Blood fluidity, fibrinogen, and cardiovascular risk factors of occlusive arterial disease: results of the Aachen study. Clin Hemorheol Microcirc 2004; 31: 185-95.
25 Szapary L. et al. Hemorheological disturbances in patients with chronic cerebrovascular diseases. Clin Hemorheol Microcirc 2004; 31: 1-9.
26 Kwaan HC. et al. Rheological abnormalities and thromboembolic complications in heart disease: spontaneous echo contrast and red cell aggregation. Semin Thromb Hemost 2003; 29: 529-34.
27 Ciuffetti G. et al. Blood rheology in men with essential hypertension and capillary rarefaction. J Hum Hypertens 2002; 16: 533-7.
28 Maresca G. et al. Measuring plasma fibrinogen to predict stroke and myocardial infarction: an update. Arterioscler Thromb Vasc Biol 1999; 19: 1368-77.
29 Danesh J. et al. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998; 279: 1477-82.
30 Rastegar R. et al. Spontaneous echo contrast videodensity is flow-related and is dependent on the relative concentrations of fibrinogen and red blood cells. J Am Coll Cardiol 2003; 41: 603-10.
31 Vaya A. et al. Erythrocyte aggregation and -455G/A polymorphism of the β-fibrinogen gene in survivors of acute myocardial infarction. Thromb Haemost 2004; 92: 223-4.
32 Rampling MW. et al. The effects of fibrinogen and its plasmin products on the rheology of erythrocyte suspensions. Clinical Hemorheology 1984; 04: 533-43.
33 Zeltser D. et al. Sex differences in the expression of haemorheological determinants in individuals with atherothrombotic risk factors and in apparently healthy people. Heart 2004; 90: 277-81.
34 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol Basel 1957; 17: 237-46.
35 International committee for standardization in hematology. Recommendation of measurement of erythrocyte sedimentation rate of human blood. Immunochemistry 1965; 02: 235-54.
36 Thomas AE. et al. Variation in the promoter region of the beta fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemost 1991; 65: 487-90.
37 Berliner S. et al. Erythrocyte adhesiveness/aggregation: a novel biomarker for the detection of lowgrade internal inflammation in individuals with atherothrombotic risk factors and proven vascular disease. Am Heart J 2005; 149: 260-7.
38 Gamzu R. et al. Increased erythrocyte adhesiveness and aggregation in peripheral venous blood of women with pregnancy-induced hypertension. Obstet Gynecol 2001; 98: 307-12.
39 Berliner AS. et al. Combined leukocyte and erythrocyte aggregation in the peripheral venous blood during sepsis. An indication of commonly shared adhesive protein(s). Int J Clin Lab Res 2000; 30: 27-31.
40 Rotstein R. et al. The picture of inflammation: a new concept that combines the white blood cell count and erythrocyte sedimentation rate into a new hematologic diagnostic modality. Acta Haematol 2001; 106: 106-14.
41 Sharshun Y. et al. Inflammation at a glance: erythrocyte adhesiveness/aggregation test to reveal the presence of inflammation in people with atherothrombosis. Heart Dis 2003; 05: 182-3.
42 Berliner S. et al. The degree of red blood cell aggregation on peripheral blood glass slides corresponds to inter-erythrocyte cohesive forces in laminar flow. Thromb Res 2004; 114: 37-44.
43 Maharshak N. et al. The erythrocyte adhesiveness/ aggregation test for the detection of an acute phase response and for the assessment of its intensity. Clin Lab Haematol 2002; 24: 205-10.
44 Zeltser D. et al. The erythrocyte adhesiveness/aggregation test (EAAT) in the peripheral blood of patients with ischemic heart and brain disease with normal fibrinogen concentrations. Appl Rheology 2000; 10: 231-7.
45 Assayag EB. et al. Inflammation-sensitive proteins and erythrocyte aggregation in atherothrombosis. Int J Cardiol 2005; 15 98: 271-6.
46 Tang Z, Tracy RP. Candidate genes and confirmed genetic polymorphisms associated with cardiovascular diseases: a tabular assessment. J Thromb Thrombolysis 2001; 11: 49-81.
47 Behague I. et al. Beta fibrinogen gene polymorphisms are associated with plasma fibrinogen and coronary artery disease in patients with myocardial infarction. Circulation 1996; 93: 440-9.
48 Maeda N. et al. Fibrinogen-induced erythrocyte aggregation: erythrocyte-binding site in the fibrinogen molecule. Biochim Biophys Acta 1987; 904: 81-91.
49 Maghzal GJ. et al. Fibrinogen B beta polymorphisms do not directly contribute to an altered in vitro clot structure in humans. Thromb Haemost 2003; 90: 1021-8.
50 Danesh J. et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA 2005; 294: 1799-809.
51 van Oijen M. et al. Fibrinogen is associated with an increased risk of Alzheimer disease and vascular dementia. Stroke 2005; 36: 2637-41.
52 Fusman G. et al. Red blood cell adhesiveness/aggregation, C-reactive protein, fibrinogen, and erythrocyte sedimentation rate in healthy adults and in those with atherosclerotic risk factors. Am J Cardiol 2002; 90: 561-3.
53 Berliner S. et al. Erythrocyte adhesiveness/aggregation: A novel biomarker for the detection of lowgrade internal inflammation in individuals with atherothrombotic risk factors and proven vascular disease. Am Heart J 2005; 149: 260-7.
54 Schechner V. et al. Comparative analysis between dextran sulfate adsorption and direct adsorption of lipoproteins in their capability to reduce erythrocyte adhesiveness/aggregation in the peripheral blood. Ther Apher Dial 2004; 08: 39-44.