Deneysel hiperlipidemi ve Apo-B konjugatı uygulamasının kan doku faktörü seviyesi ve karaciğer doku faktörü aktivitesi üzerine etkileri
Amaç: Hiperlipidemi ve hiperkoagülasyon ateroskleroz gelişiminde önemli yer tutar. Aterom plakları içinde özellikle yüksek miktarda Apolipoprotein-B 100 (Apo-B) içeren LDL-C (düşük dansiteli lipoprotein kolesterolü) görülmektedir. Bu nedenle deneysel hiperlipidemi oluşturulan sıçanlarda ve Apo-B konjugatı uygulamasının kandaki doku faktörü (DF) miktarı ve karaciğer DF aktivitesi üzerine etkilerini incelemeyi amaçladık. Yöntem: Bu çalışmada deneysel Apo-B konjugatı ilaveli ve ilavesiz deneysel hiperlipidemi yapılan 32 adet C57BL/6 türü fare her bir grupta 8 fare olacak şekilde 3 gruba ayrıldı (1-Kontrol grubu; 2-Hiperlipidemi grubu; 3-Hiperlipidemi + Apo-B grubu). İki ay sonunda sakrifiye edilen hayvanların rutin lipid parametreleri, kanda ve karaciğer dokusunda doku faktörü (DF) miktarı ve aktivitesi incelendi. Bu amaçla total lipid miktarı, fosfovanilin metodu ile, total ve LDL kolesterol ticari kit kullanılarak, kan DF tayini ELISA yöntemi ile, karaciğer DF aktivitesi ise Quick metodu ile ölçüldü. Bulgular: Hiperlipidemik grupta total lipid, kolesterol, LDL-C değerleri kontrol grubuna göre anlamlı olarak arttı; LDL-C değeri Apo- B konjugatı ilave edilen grupta azalırken, total lipid ve total kolesterol değerleri arttı. Kandaki DF değerleri anlamlı bir artış gösterdi; Apo-B konjugatı verilen grupta kandaki DF sonuçları değişmedi. Karaciğer homojenatında DF aktivitesi hiperlipidemik grupta hızlandı; Apo- B verilen grupta sonuç değişmedi.Sonuç: Elde ettiğimiz sonuçlar biyokimyasal yönden değerlendirildiğinde, ateroskleroz patogenezinde önemli olduğu düşünülen hiperlipidemi ve hiperkoagülasyon durumunda Apo-B konjugatı uygulamasının etkili olduğu görülmüştür. Ancak bu konudaki çalışmaların Apo-B konjugatı enjeksiyonunun immunülojik yönlerinin de detaylandırılarak devam etmesinde yarar olduğunu düşünmekteyiz.
Anahtar Kelimeler:
Deneysel hiperlipidemi, C57BL/6, Apo-B 100, doku faktörü
Effects of experimental hyperlipidemia and Apo-B conjugate administration on blood tissue factor level and the tissue factor activity of liver
Objective: Hyperlipidemia and hypercoagulation are the major risk factors in atherosclerotic events. Low density lipoproteins (LDLs) are the main source of lipids in the athresclerotic plaques within the foam cells. Apoprotein B-100 (Apo-B) is the main protein in the LDL- cholesterol (LDL-C). For this purpose we aimed to investigate blood tissue factor (TF) levels and the TF activity of liver in experimental hyperlipidemia with and without Apo-B conjugate administration.Methods: Thirty two C57BL/6 mice were divided into 3 groups as control group (n=8), hyperlipidemic group (n=8), hyperlipidemic+Apo-B group (n=8). Mice were sacrified at the end of two months and blood lipid parameters, blood TF levels and TF activity of liver were investigated. Serum lipid parameters were determined by using commercial kits, blood TF levels were determined by Elisa and liver TF activities were measured by Quick method.Results: Serum levels of total lipid, cholesterol, LDL-C significantly increased in hyperlipidemic group; LDL-C significantly decreased in both Apo-B and LDL conjugate given hyperlipidemic groups. Serum TF increased significantly in short term hyperlipidemia, TF activities in the liver homogenate also increased significantly. There was no effect of Apo-B conjugates on TF values in blood and liver homogenate. Conclusion: Based on the results of this study Apo-B conjugate administration was effective in hyperlipidemia and hypercoagulation which are important factors in atherosclerosis. On the other hand we believe that new studies are necessary to investigate immunological properties of Apo-B conjugate administration.
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- Ulutin ON. The relationship of haemostatic system to the vessel wall, thromboembolism, atherosclerosis from pathogenesis and laboratory standpoints Turk J Haematol 2002; 19: 7-29.
- Emekli N. Hemostatik sistemin dünü ve bugünü. İçinde: Temel ve Uygulamalı Biyokimya sayfa.445-458, 4. Baskı, Akademi Matbaası, İstanbul, Marmara Yayınları, 2006.
- Libby P, Theroux P. Pathophysiology of Coronary Artery Disease. Circulation 2005; 111: 3481-3488.
- Emekli N. Koagulasyon ve İnflamasyon. Tromboz Hemostaz ve Anjioloji Kongre Kitabı Editör Orhan N. Ulutin, sayfa 69-77, İkite Matbacılık Hizmetleri, İstanbul, 2004.
- Ding L, Ma Wanahu, Littmann T, Camp R, Shen J. The PfY2 nucleotide receptor mediates tissue factor expression in human coronary artery endothelial cells. JBC 2011; 235176:1-20.
- Handsson GK: Inflammation, atherosclerosis, and coronary artery disease. N Eng J Med. 2005; 352: 1685-1695.
- Emekli-Alturfan E, Başar I, Malalı E, Elemek E, Oktay S, Ayan F, Emekli N, Noyan U. Plasma tissue factor levels and salivary tissue fakcor activities of periodontitis patient with and without cardiovascular disease. Pathophysiol Haemost Thromb. 2009; 37(2-4):77-81.
- Andrea DD, Ravera M, Golino P, Rosica A, Felice M, Raagni M, CirilloP, Vigorito F, Corcione N, Tommasini P, Gargiulo A, Piro O, Calabro, Chiariello M. Induction of tissue factor in the arterial wall during recurrent thrombus formation. Arterioscler Thromb Vasc Biol. 2003;23: 1689-1694.
- George J, Shoenfeld Y, Afek A, Gilburd B, Keren P, Shanish A, Kopolovic J, Wick G, Harats D. Enhanced fatty streak formation in C57BL/6J Mice by immunization with heat shock protein-65. Arterioscler Thromb Vasc Biol. 1999; 19:505-510.
- Yarat A. Sepsis ve doku faktörü.7.Tromboz, Hemostaz ve Anjioloji Kongre Kitabı. Editör. Orhan N. Ulutin, Sayfa 375-393, İkite Matbaacılık, İstanbul, 2007.
- Reganon E, Vila V, Martinez – Sale V, Vaya A, Aznar J. Inflammation, fibrinogen and thrombin generation in patients with previous myocardial Rinfarction. Haematologica 2002; 87:740-745.
- Sebuski RJ, Kilgore KS. Role of inflammatory mediators in thrombogenesis. J Pharmacol Exp Ther. 2002; 300:729-735.
- Koba S, Tanaka H, Maruyama C, Tada N, Birou S, Teramoto T, Sasaki J. Physical activity in the Japan population: association with blood lipid levels and effects in reducing cardiovascular and all-cause mortality. J Atheroscler Thromb. 2011; 18(10):833-45.
- Emekli N. Biochemical Aspects of Haemostasis. In:Basic and Applied Biochemistry. Sayfa:341-417, Marmara Üniversitesi Yayınları No.556, Dişhekimliği Fakültesi Yayın No.3. İstanbul, 1994.
- Day SM, Reeve Jl, Pederson B, Farris DM, Myers DD, Im M, Wakelfield TW, Mackman N,Fay WP . Macrovascular thrombosis is driven by tissue factor derived primarily from primarily from the blood vessel wall. Blood 2005; 105:192-198.
- Bochli E. Historical review: History of tissue factor. Br J Haematol. 2000; 110:248-255.
- Yarat A. Tromboplastik Aktivite. IV. Tromboz, Hemostaz ve Anjioloji Kongre Kitabı. Editör Orhan N. Ulutin , sayfa 97-105, May Matbacılık Lt.Şti. İstanbul, 2003.
- Tunali T, Yarat A, Bulut M, Emekli N. 6,7-Dihydroxy-3-phenylcoumarin inhibits thromboplastin induced disseminated intravascular coagulation. Br J Haematol. 2004; 126(2): 226-30.
- Emekli NB, Ulutin ON.Some properties of autoprothrombin II-A anticoagulant, Recent Progress in Blood Coagulation and Thrombosis Research. Biblith Haem. 1978; 44:15.
- Mackman N, Taubman M. Tissue factor: past, present and future. Arterioscler Thromb Vasc Biol. 2009; 29:1986-1988.
- Bakarewa MI, Morrissey JH, Tarkowski A. Tissue factor as aproinflammatory agent. Arthritis Res. 2002; 4:190-195.
- Fregula CF, Marchese P, Gruber A, Ruggeri ZM, Ruf W. P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin.Invest. 2000; 7:2932-2944.
- Roselar SE, Schonfeld G, Daugherty A, Enhanced development of atherosclerosis in cholesterol fed rabbits by suppression of cell mediated immunity. J Clin Invest.1995; 96:1389-94.
- Hulthe J, Wiklund O, Camejo HE, Bondjers G.Antibodies to oxidized LDL in relation to carotid atherosclerosis, cell adhesion molecule and phospholipase A2. Arterioscler Thromb Vasc Biol. 2001; 21:269-274.
- Kjalke M, Silveira A, Hamsten A, Hedner U, Ezban M. Plasma lipoproteins enhance tissue factor-independent factor VII activation. Arterioscler Thromb Vasc Biol. 2000; 20:1835- 1841.
- Butenas S, Orfeo T, Mann K. Tissue factor in coagulation: Which? Where? When?. Arterioscler Thromb Vasc Biol. 2009; 29:1989-1996.
- Pan Shuchong, White TA, Witt TA, Chiriac A, Mueske CS, Simari RD. Vascular directed tissue factor pathway inhibitor overexpression regulates plasma cholesterol and reduces atherosclerotic plaque development. Circ Res. 2009; 105:713-720.
- Silveira A, Karpe F, Johnson H, Bauer KA, Hamsten A. In vivo demonstration in humans that large postprandial triglyceride rich lipoproteins activate coagulation factor VII through the intrinsic coagulation pathway. Arterioscler Thromb Vasc Biol. 1996; 16:1333- 1339.
- Mayer MP, Tracy RP, Tracy PB, van’t Veer C, Sparks CE, Mann KG. Plasma lipoproteins support prothrombinase and other procoagulant enzymatic complexes. Arterioscler Thromb Vasc Biol. 1998; 18:458- 465.
- Mitropoulos KA, Miller GJ, Reeves BEA, Wilkes HC, Cruickshank JK. Factor VII coagulant activity is stongly associated with the plasma concentration of large lipoprotein particles in middle aged men. Atherosclerosis. 1989; 76:203-208.
- Xu N, Dahlback B, Ohlin AK, Nilsson A. Association of vitamin K dependent coagulation proteins and C4b binding protein with triglyceride risch lipoproteins of human plasma. Arterioscler Thromb Vasc Biol. 1998; 18:33-39.
- Schwartz BS, Levy GA, Curtiss LK, Fair DS, Edgington TS. Plasma lipoprotein induction and suppression of the generation of cellular procoagulant activity in vitro. J Clin Invest. 1981; 67:1650-1658.
- Wada H, Kaneko T, Wakita Y, Minamikawa K, Nagaya S, Tamaki S, Deguchi K, Shirakawa S. Effect of lipoproteins on tissue factor activity and PAI-II antigen in human monocytes and macrophages. Int J Cardiol. 1994; 47:521-525.
- Yayın Aralığı: Yılda 4 Sayı
- Başlangıç: 2011
- Yayıncı: Marmara Üniversitesi
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