Arteriosclerosis and Thrombosis, Vol 13, 1738-1742, Copyright © 1993 by American Heart Association

ARTICLES

Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin

R Lassila, S Peltonen, M Lepantalo, O Saarinen, P Kauhanen and V Manninen
Wihuri Research Institute, Helsinki, Finland.

Immunohistochemical studies of human atherosclerotic lesions have demonstrated the occurrence of fibrin deposition and its degradation in the arterial wall. We studied fibrinogen, the generation of thrombin, and the degradation of fibrin in 40 patients with stable peripheral arterial occlusive disease of varying severity, as assessed by the ankle/brachial pressure index and duplex ultrasonography and/or angiography. Circulating fibrinogen (functional and immunological), fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer were measured. The severity of atherosclerosis was associated with both fibrinogen (both functional and immunological) and D-dimer (r = .57, P < .0002, and r = .57, P < .0001, respectively). Fibrinogen and D-dimer showed a significant positive correlation (r = .50, P < .001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antithrombin III complex. As a sign of coagulation activation and fibrinolysis, we found that thrombin- antithrombin III complex and the degradation of cross-linked fibrin were progressively associated with the extent of vascular disease. The plasmin-mediated fibrin breakdown contributed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations between fibrinogen/D-dimer and the severity of atherosclerosis support previous pathological studies and imply that local degradation of cross-linked fibrin is involved in the progression of atherosclerosis.

This article has been cited by other articles:

				A. P. L. Mota, M. E. R. de Castro Santos, F. d. C. Lima e Silva, N. C. de Carvalho Schachnik, M. de Oliveira Sousa, and M. das Gracas Carvalho Hypercoagulability Markers in Patients With Peripheral Arterial Disease: Association to Ankle-brachial Index Angiology, October 1, 2009; 60(5): 529 - 535. [Abstract] [PDF]

				A. de Giorgio-Miller, S. Bottoms, G. Laurent, P. Carmeliet, and S. Herrick Fibrin-Induced Skin Fibrosis in Mice Deficient in Tissue Plasminogen Activator Am. J. Pathol., September 1, 2005; 167(3): 721 - 732. [Abstract] [Full Text] [PDF]

				C. Monaco, E. Rossi, D. Milazzo, F. Citterio, F. Ginnetti, G. D'Onofrio, D. Cianflone, F. Crea, L. M. Biasucci, and A. Maseri Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden J. Am. Coll. Cardiol., January 18, 2005; 45(2): 238 - 243. [Abstract] [Full Text] [PDF]

				C. Vadseth, J. M. Souza, L. Thomson, A. Seagraves, C. Nagaswami, T. Scheiner, J. Torbet, G. Vilaire, J. S. Bennett, J.-C. Murciano, et al. Pro-thrombotic State Induced by Post-translational Modification of Fibrinogen by Reactive Nitrogen Species J. Biol. Chem., March 5, 2004; 279(10): 8820 - 8826. [Abstract] [Full Text] [PDF]

				A. P. Simopoulos Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases J. Am. Coll. Nutr., December 1, 2002; 21(6): 495 - 505. [Abstract] [Full Text] [PDF]

				A.L. Komarov, E.P. Panchenko, A.B. Dobrovolsky, Yu.A. Karpov, A.D. Deev, E.V. Titaeva, K.K. Davletov, A.R. Eshkeeva, and L.A. Markova D-dimer and platelet aggregability are related to thrombotic events in patients with peripheral arterial occlusive disease Eur. Heart J., August 2, 2002; 23(16): 1309 - 1316. [Abstract] [PDF]

				A. Makin, S.H. Silverman, and G.Y.H. Lip Peripheral vascular disease and Virchow's triad for thrombogenesis QJM, April 1, 2002; 95(4): 199 - 210. [Full Text] [PDF]

				T. Iwaki, M. J. Sandoval-Cooper, M. Paiva, T. Kobayashi, V. A. Ploplis, and F. J. Castellino Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse Am. J. Pathol., March 1, 2002; 160(3): 1021 - 1034. [Abstract] [Full Text] [PDF]

				W. Koenig, D. Rothenbacher, A. Hoffmeister, M. Griesshammer, and H. Brenner Plasma Fibrin D-Dimer Levels and Risk of Stable Coronary Artery Disease: Results of a Large Case-Control Study Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1701 - 1705. [Abstract] [Full Text] [PDF]

				A. Woods, D.J. Brull, S.E. Humphries, and H.E. Montgomery Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6 Eur. Heart J., October 1, 2000; 21(19): 1574 - 1583. [PDF]

				V. A. Ploplis, J. Wilberding, L. McLennan, Z. Liang, I. Cornelissen, M. E. DeFord, E. D. Rosen, and F. J. Castellino A Total Fibrinogen Deficiency Is Compatible with the Development of Pulmonary Fibrosis in Mice Am. J. Pathol., September 1, 2000; 157(3): 703 - 708. [Abstract] [Full Text] [PDF]

				M.-C. Tataru, J. Heinrich, R. Junker, H. Schulte, A. von Eckardstein, G. Assmann, and E. Koehler D-dimers in relation to the severity of arteriosclerosis in patients with stable angina pectoris after myocardial infarction Eur. Heart J., October 2, 1999; 20(20): 1493 - 1502. [Abstract] [PDF]

				M. Tschopl, D. A. Tsakiris, G. A. Marbet, K.-H. Labs, and K. Jager Role of Hemostatic Risk Factors for Restenosis in Peripheral Arterial Occlusive Disease After Transluminal Angioplasty Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3208 - 3214. [Abstract] [Full Text]

				L. V. Lee, G. A. Ewald, C. R. McKenzie, and P. R. Eisenberg The Relationship of Soluble Fibrin and Cross-linked Fibrin Degradation Products to the Clinical Course of Myocardial Infarction Arterioscler Thromb Vasc Biol, April 1, 1997; 17(4): 628 - 633. [Abstract] [Full Text]

				Y. Jang, L. A. Guzman, A. M. Lincoff, M. Gottsauner-Wolf, F. Forudi, C. E. Hart, D. W. Courtman, M. Ezban, S. G. Ellis, and E. J. Topol Influence of Blockade at Specific Levels of the Coagulation Cascade on Restenosis in a Rabbit Atherosclerotic Femoral Artery Injury Model Circulation, November 15, 1995; 92(10): 3041 - 3050. [Abstract] [Full Text]

				J. Levenson, P. Giral, M. Razavian, J. Gariepy, and A. Simon Fibrinogen and Silent Atherosclerosis in Subjects With Cardiovascular Risk Factors Arterioscler Thromb Vasc Biol, September 1, 1995; 15(9): 1263 - 1268. [Abstract] [Full Text]

				A. J. Lee, F. G. R. Fowkes, G. D. O. Lowe, and A. Rumley Determinants of Fibrin D-Dimer in the Edinburgh Artery Study Arterioscler Thromb Vasc Biol, August 1, 1995; 15(8): 1094 - 1097. [Abstract] [Full Text]

				G. S. Retzinger Adsorption and Coagulability of Fibrinogen on Atheromatous Lipid Surfaces Arterioscler Thromb Vasc Biol, June 1, 1995; 15(6): 786 - 792. [Abstract] [Full Text]