Endocardial Changes in Nonvalvular Atrial Fibrillation Without Atrial Thrombus-Thrombomodulin and Tissue Factor Pathway Inhibitor

Overview

Journal Clin Appl Thromb Hemost

Publisher Sage Publications

Specialty Cardiology & Vascular Diseases

Date 2018 Jan 25

PMID 29364003

Citations 4

Authors

Kang An

Ju Mei

Jiaquan Zhu

Min Tang

Affiliations

Soon will be listed here.

Abstract

Atrial fibrillation (AF) is a well-known cause for thromboembolism. Although blood stasis in the left atrium and hypercoagulable state of the blood have been emphasized as important mechanisms, limited attention has been paid to the endocardial changes in maintaining the balance of local coagulation, which may also contribute to the thrombus formation in AF. In the present study, left atrial appendage samples were obtained at heart surgery from nonvalvular AF and non-AF patients without atrial thrombus. Immunohistochemistry for endocardial markers including thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI) was performed and semiquantitatively graded. In immunohistochemistry analysis, decreased expression of TM was found in patients with nonvalvular AF compared with those without AF ( P < .001). There was no difference in TFPI expression between the 2 groups ( P = .213). Patients with TM score of 0 or 1 seemed to have larger left atrial diameter (LAD) than those with TM score of 2 or 3 (44.0 (7.9) vs 40.6 (3.9); P = .009), while no relationship between LAD and TFPI expression was found (43.4 (7.0) vs 42.9 (7.8); P = .485). In conclusion, TM expression in the atrial endocardium is decreased in nonvalvular AF without atrial thrombus, while TFPI expression is not. Downregulated TM expression might be associated with enlarged LAD.

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References

Gosling M, Golledge J, Turner R, Powell J . Arterial flow conditions downregulate thrombomodulin on saphenous vein endothelium. Circulation. 1999; 99(8):1047-53. DOI: 10.1161/01.cir.99.8.1047. View

Lester S, RYAN E, Schiller N, Foster E . Best method in clinical practice and in research studies to determine left atrial size. Am J Cardiol. 1999; 84(7):829-32. DOI: 10.1016/s0002-9149(99)00446-4. View

Obel O, Camm A . Left atrial appendage: structure, function, and role in thromboembolism. Heart. 1999; 82(5):547-54. PMC: 1760793. DOI: 10.1136/hrt.82.5.547. View

Sagripanti A, Carpi A . Antithrombotic and prothrombotic activities of the vascular endothelium. Biomed Pharmacother. 2000; 54(2):107-11. DOI: 10.1016/S0753-3322(00)88861-7. View

Li-Saw-Hee F, Blann A, Lip G . A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation. J Am Coll Cardiol. 2000; 35(7):1926-31. DOI: 10.1016/s0735-1097(00)00627-6. View

Goldsmith I, Kumar P, Carter P, Blann A, Patel R, Lip G . Atrial endocardial changes in mitral valve disease: a scanning electron microscopy study. Am Heart J. 2000; 140(5):777-84. DOI: 10.1067/mhj.2000.110284. View

Golino P, Ragni M, Cimmino G, Forte L . Role of tissue factor pathway inhibitor in the regulation of tissue factor-dependent blood coagulation. Cardiovasc Drug Rev. 2002; 20(1):67-80. DOI: 10.1111/j.1527-3466.2002.tb00083.x. View

Chung N, Belgore F, Conway D, Blann A, Lip G . Is the hypercoagulable state in atrial fibrillation mediated by vascular endothelial growth factor?. Stroke. 2002; 33(9):2187-91. DOI: 10.1161/01.str.0000023889.84649.3d. View

Tsang T, Gersh B, Appleton C, Tajik A, Barnes M, Bailey K . Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women. J Am Coll Cardiol. 2002; 40(9):1636-44. DOI: 10.1016/s0735-1097(02)02373-2. View

10.

Sperry J, Deming C, Bian C, Walinsky P, Kass D, Kolodgie F . Wall tension is a potent negative regulator of in vivo thrombomodulin expression. Circ Res. 2003; 92(1):41-7. DOI: 10.1161/01.res.0000048196.11060.a0. View

11.

Walker F, Fay P . Regulation of blood coagulation by the protein C system. FASEB J. 1992; 6(8):2561-7. DOI: 10.1096/fasebj.6.8.1317308. View

12.

Tsang T, Barnes M, Gersh B, Takemoto Y, Rosales A, Bailey K . Prediction of risk for first age-related cardiovascular events in an elderly population: the incremental value of echocardiography. J Am Coll Cardiol. 2003; 42(7):1199-205. DOI: 10.1016/s0735-1097(03)00943-4. View

13.

Yamashita T, Sekiguchi A, Iwasaki Y, Sagara K, Hatano S, Iinuma H . Thrombomodulin and tissue factor pathway inhibitor in endocardium of rapidly paced rat atria. Circulation. 2003; 108(20):2450-2. DOI: 10.1161/01.CIR.0000102969.09658.F2. View

14.

Nakamura Y, Nakamura K, Fukushima-Kusano K, Ohta K, Matsubara H, Hamuro T . Tissue factor expression in atrial endothelia associated with nonvalvular atrial fibrillation: possible involvement in intracardiac thrombogenesis. Thromb Res. 2003; 111(3):137-42. DOI: 10.1016/s0049-3848(03)00405-5. View

15.

Thambidorai S, Murray R, Parakh K, Shah T, Black I, Jasper S . Utility of transesophageal echocardiography in identification of thrombogenic milieu in patients with atrial fibrillation (an ACUTE ancillary study). Am J Cardiol. 2005; 96(7):935-41. DOI: 10.1016/j.amjcard.2005.05.051. View

16.

Kapur N, Deming C, Kapur S, Bian C, Champion H, Donahue J . Hemodynamic modulation of endocardial thromboresistance. Circulation. 2006; 115(1):67-75. DOI: 10.1161/CIRCULATIONAHA.106.640698. View

17.

Bangalore S, Yao S, Chaudhry F . Role of left atrial size in risk stratification and prognosis of patients undergoing stress echocardiography. J Am Coll Cardiol. 2007; 50(13):1254-62. DOI: 10.1016/j.jacc.2007.06.025. View

18.

Hughes M, Lip G . Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost. 2008; 99(2):295-304. DOI: 10.1160/TH07-08-0508. View

19.

Burstein B, Nattel S . Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol. 2008; 51(8):802-9. DOI: 10.1016/j.jacc.2007.09.064. View

20.

Knackstedt C, Gramley F, Schimpf T, Mischke K, Zarse M, Plisiene J . Association of echocardiographic atrial size and atrial fibrosis in a sequential model of congestive heart failure and atrial fibrillation. Cardiovasc Pathol. 2008; 17(5):318-24. DOI: 10.1016/j.carpath.2007.12.003. View