Importance of apopitosis markers and oxidized low density lipoprotein for diagnosis and prognosis determination of acute myocardial infarction

Gündüz Ayhan Erener, Mehmet Yazıcı, Rahim Kocabaş, Mehmet Aköz
2.727 298

Öz


Akut miyokard infarktüsü teşhisi ve prognozunu belirlemede CK-18, HSP70, H-FABP ve Ox-LDL gibi biyokimyasal belirteçlerin önemini, aralarındaki korelasyonu ve CK-MB, TROPONİN I gibi bilinen kardiyak parametrelere karşı üstünlükleri olup olmadığını belirlemek amaçlanmıştır.Çalışma; semptomlar başladıktan 6 saat içinde acile başvuran ve giriş troponin değerleri yüksek, ilk defa Mİ geçiren 45-65 yaş arası 40 erkek bireyden alınan kanlar üzerinde gerçekleştirilmiştir. Bu hastaların ilk başvuruda, 24. saat ve 30.gün sonrasında venöz kan örnekleri toplanmıştır. Bu parametrelerin sağlıklı bireylerdeki referans aralığının belirlenebilmesi amacıyla, hasta grubumuzla benzer yaş ve cinsiyet dağılımı gösteren 30 sağlıklı gönüllü erkek bireyden de bir defaya mahsus kan örnekleri alınmıştır. Gruplar; grup I (Girişteki kan değerleri), grup II (24. saat kan değerleri), grup III (30. gün kan değerleri) ve grup IV (Kontrol grubu kan değerleri) şeklinde düzenlenmiştir. HSP70, CK-18, H-FABP ve Ox-LDL düzeyleri ELİSA tekniği ile çalışan ticari kitlerle, CK-MB ve TroponinI parametreleri ise kemilüminesan esaslara göre ölçülmüştür.Hastaların girişteki kan değerlerine bakıldığında:  HSP70, H-FABP ve Ox-LDL' nin; 24. saatteki değerler için HSP70 ve H-FABP' nin ve 30. gün kan değerleri için ise CK-18, Ox-LDL ve HSP70' in kontrol grubundaki değerlere oranla önemli düzeyde yüksek ve istatistiksel olarak anlamlı olduğu görülmüştür. HSP70 ve cTnI arasında pozitif korelasyon olduğu saptanmıştır.Bulgularımız; H-FABP' nin AMI'nün erken teşhisi için tanısal doğruluğa sahip olduğunu, Ox-LDL' nin AMI için önemli bir risk faktörü olduğunu, MI erken teşhisinde periferal kanda tepitiyle tanıyı kuvvetlendirebileceğini, MI sonrası antioksidan tedavinin de gerekli olabileceğini, HSP70' in MI teşhisinde cTnI ile beraber tanısal doğruluğu artırmakta olduğunu ve prognostik değer taşıdığını, CK-18' in iskemi reperfüzyon sonucu mikrovasküler endotelial dokudan salgılanarak kan serum seviyelerinin tespit edilebilir olduğunu fakat AMI erken teşhisinde tanısal doğruluğu göstermede yeterli olamayacağını göstermiştir.

Anahtar kelimeler


FABP3 proteini, akut koroner sendrom, HSP70, kreatin kinaz, troponin I, okside düşük dansiteli lipoprotein, m30 sitokeratin-18 peptit

Tam metin:

PDF (English)

Referanslar


Abstracts of the 39. Annual Conference on Cardiovascular Disease Epidemiology and Prevention.Circulation 1999;14:1-170.

Heper C, Heper Kardiyoloji, Nobel & Güneş Tıp Kitabevi 2002;225-254.

Tp Singh, Ak Nigam, Ak Gupta, B Singh Cardiac Biomarkers: When to Test? – Physician Perspective Journal, Indian Academy of Clinical Medicine z Vol. 12, No. 2 z April-June, 2011: 117-121

Sonel A, Sonel Kardiyoloji,Semih Ofset Ltd.Sti. 4.Baskı 2003; 558-601.

Rylander L, Ziegler E, Bergman T, Schöberl E, Steiner G, et al. Molecular characterization of a tissue-polypeptide-spesific-antigen epitope and its relationship to human cytokeratin 18. Eur J Biochem 1996; 241:309-314.

G.Kramer, H.Erdal, HJ.Mertens, M.Nap, J.Maurmann, et al.Differentiation between cell death modes using measurements ofdifferent soluble forms of extracellular cytokeratin 18, Cancer Res 2004; 64: 1751-1756.

Ueno T, Toi M, Biven K, Bando H, Ogawa T, Linder S. Measurement of an apoptotic product in the sera of breast cancer patient. Eur J Cancer 2003; 39:769-774.

Ulukaya E, Yilmaztepe A, Akgoz S, Linder S, Karadag M. The levels of caspase-cleaved cytokeratin 18 are elevated in serum from patients with lung cancer and helpful to predict the survival. Lung Cancer. 56:399-404, 2007.

Barak V., Goike H., Panaretakis W.K, Einarsson R., Clinical utility of cytokeratins as tumor markers. Clin Biochem 2004;37: 529-540.

McDouall RM, Yacoub M, Rose ML. Isolation, culture, and characterisation of MHC class II-positive microvascular endothelial cells from the human heart. Microvasc Res 1996; 51:137–152.

Mattey DL, Dawes PT, Nixon NB, Goh L, Banks MJ, Kitas GD. Increased levels of antibodies to cytokeratin 18 in patients with rheumatoid arthritis and ischaemic heart disease. Ann Rheum Dis 2004; 63:420–425.

Adlbrecht C, Hoetzenecker K, Posch M, Steiner S, Kopp C, Hacker S, et al. Elevated levels of

interleukin-1beta-converting enzyme and caspase-cleaved cytokeratin-18 in acute myocardial infarction. Eur J Clin Invest 2007; 37:372–380.

Aşkar, T.K., Ergün, N. ve Turunç, V., Isı şok proteinler ve fizyolojik rolleri, Kafkas Üniv Vet Fak Dergisi 2007;109-114.

Zügel U, Kaufmann SH. Role of heat shock proteins in protection from and pathogenesis of

infectious diseases. Clin Microbiol Rev 1999; 12: 19-39.

Garrido C, Gurbuxani S, Ravagnan L, Kroemer G. Heat shock proteins: endogenous modulators of apoptotic cell death. Biochem Biophys Res Commun 2001; 286:433-442.

Li, C.Y., Lee, J.S., Ko, Y.G., Kim, J.I. and Seo, J.S.,Heat shock protein 70 inhibits apoptosis downstream of cytochrome c release and upstream of caspase-3 activation, J Biol Chem 2000;275:25665-25671.

Börchers T, Unterberg C, Rüdel H, Robenek H. Spener F. Subcellular distribution of cardiac fatty acid binding protein in bovine heart muscle and quantitation with an enzyme-linked immunosorbent assay. Biochimica et Biophysica Acta 1989; 1002: 54-61.

Schaap FG, Van der Vusse GJ, Glatz JF. Fatty acid binding proteins in the heart. Molecular and Cellular Biochemistry 1998; 180: 43-51.

Watanabe M, Ono T, Kondo H. Immunohistochemical studies on the localisation and ontogeny

of heart fatty acid binding protein in the rat. J Anat 1991; 174: 81-95.

Alhadi HA, Fox KAA. Do we need additional markers of myocyte necrosis?:the potential value of heart fatty acid binding protein. Q J Med. 2004;97:187-198.

Meng X, Ming M, Wang E. Heart fatty acid binding protein as a marker for postmortem detection of early myocardial damage. Forensic Science International 2006;160: 11-16.

Ishii J, Wang JH, Naruse H, Taga S, Kinoshita M, et al. Serum concentration of myoglobin vs human heart-type cytoplasmic fatty acid binding protein in early detection of acute myocardial infarction. Clin Chem. 1997;43:1372-1378.

Mair J. Progress in myocardial damage detection: New biochemical markers for clinicians. Crit Rev Clin Lab Sci 1997; 34:1-66.

Orak M, Ustündağ M, Güloğlu C, Ozhasenekler A, Alyan O, Kale E. The role of the heart-type fatty acid binding protein in the early diagnosis of acute coronary syndrome and its comparison with troponin I and creatine kinase-MB isoform. Am J Emerg Med. 2010; 28:891-896.

Liao J, Chan CP, Cheung YC, Lu JH, Luo Y, Cautherley GW, Glatz JF, et al. Human heart-type fatty acid-binding protein for on-site diagnosis of early acute myocardial infarction. Int J Cardiol. 2009;133:420-423.

Özekin A, Değer O,LDL Oksidasyonu ve Etkileri. İbni Sina Tıp Dergisi 2001;6:125-132.

Murphy J.E.,Tedburry P.R.,Homer-Vanniasinkam S.,WalkerJ.H., Ponnambalam S. Biochemistry and cell biology of mamalian scavenger reseptors. Aterosclerosis 2005; 182:1-15.

Witztum JL. İmmunologial response to oxidized LDL. Atherosclerosis 1997;131: 9-11.

Esterbauer H, Dieber-Rotheneder M, Waeg G, Striegl G, Jurgens G. Biochemical, structural and functional properties of oxidised low-density lipoproteins. Chemical Research in Toxicology 1990;3:77-91.

Leake DS. Does an acidic pH explain why low-density lipoproteins is oxidized in atherosclerotic lesions. Atherosclerosis 1997; 129:149-157.

Fogelman AM, Haberland ME, Seager J. Factors regulating the activites of the low density lipoprotein receptor and the scavenger receptoron human monocyte-macrophages. J Lipid Res1981; 22:1131-1141.

Steinberg D, Witztum JL. Lipoproteins and Atherogenesis. Current Concepts. JAMA 1990; 264: 3047-3052.

Morin RJ, Peng S. The Role of Cholesterol Oxidation Products in The Pathogenesis of Atherosclerosis. An Clin Lab Sci.1989;19: 225-237.

Halliwel B. Free radicals, reactive oxygen species and human disease: a critical evaluation with special reference to atherosclerosis. Br J Exp.Pathol 1989; 70: 737-757.

Holvoet P. Role of oxidatively modified low density lipoproteins and anti-oxidants in atherothrombosis. Expert. Opin. İnvestig. Drugs 1999;8: 527-544.

Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ. Induction of endothelial cell expression of granulocyte and macrofage colony stimulating factors by modified low-density lipoproteins. Nature 1990; 344: 254-257.

Şahin İ. Koroner Arter Hastalarında Postprandiyal Glisemi ile Gensini Skoru ile Bakılan Koroner Arter Hastalıgı Ciddiyetinin İlişkisi(Uzmanlık Tezi).Siyami Ersek Eğitim Ars.Hastanesi 2006.

Rajappa M, Sharma A. Biomarkers of cardiac injury: An update. Angiology 2005; 56:677-691.

Kiess W, Gallaher B. Hormonal control of programmed cell death apoptosis. Eur J Endocrin 1998;18: 482-491.

Hetts S W. To die or not to die: An overview of apoptosis and its role in disease. JAMA 1998;278: 300-307.

Haastrup B, Gill S, Kristensen SR, Jorgensen PJ, Glatz JF, et al. Biochemicai markers of ischaemia for the early identification of acute myocardial infarction without ST segment elevation. Cardiology 2000; 94:254-261.

Okamoto F, et all. Human heart type cytoplasmic fatty acid binding protein fort he diagnosis of acute myocardial infarction. Clinical evulation of H-FABP in comprasion with myoglobin and creatine kinase isoenzyme MB. Clin Chem Lab Med 2000; 38:231-238.

Figiel L, Wraga M, Bednarkiewicz Z, Lipiec P, Smigielski J, Krzemińska-Pakuła M, Kasprzak JD. Direct comparison of the diagnostic value of point-of-care tests detecting heart-type fatty acid binding protein or glycogen phosphorylase isoenzyme BB in patients with acute coronary syndromes with persistent ST-segment elevation. Kardiol Pol. 2011;69:1-6.

Carl A.Burtis,Edward R.Ashwood,Klinik Kimyada Temel İlkeler,Tietz 5. Baskı,Palme Yayıncılık 2005; 688-694.

Hafidh A Alhadi1 and Keith A A Fox2 . Heart-Type Fatty Acid-Binding Protein in the Early Diagnosis of Acute Myocardial Infarction The potential for influencing patient management . SQU Med J 2010;10 :141-149.

Glatz JFC, Haastrup B, Hermens WT, et al. Fatty acid binding protein and the early detection of acute myocardial infarction:the EUROCARDI multicenter trial.Circulation 1997;96:215 (abstract)

Okamoto F, Sohmiya K, Ohkaru Y, et al. Human heart-type cytoplasmic fatty acid binding protein for the diagnosis of acute myocardial infarction. Clinical evaluation of h-FABP in comparison with myoglobin and creatine kinase isoenzyme MB. Clin Chem Lab Med 2000;38:231-238.

.Ghani F, Wu AHB, Graff L, et al. Role of heart-type fatty acid-binding protein in early detection of acute myocardial infarction. Clin Chem 2000;46:718-719.

Shimada K, Mokuno H, Masunaga E, Miyazaki T, Sumiyoshi K, Miyauchi K, Diada H. Circulating oxidized low-density lipoprotein is an independent predictor for cardiac event in patients with coronary artery disease. Atherosclerosis 2004;174:343-347.

Demirbağ R, Yılmaz R, Koçyiğit A. Relationship between DNA damage, total antioxidant capacity and coronary artery disease. Mutat Res 2005;570:197-203.

Fredrikson GN, B. Hedblad B, Berglund G, Nilsson J. Plasma oxidized LDL: a predictor for acute myocardial infarction? J İn Medi 2003;253:425-429.

Zhang X., Xu Z., Zhou L., Chen Y., He M., Cheng L. , Hu F. B., Tanguay R. M. , Wu T. Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome. Cell Stress and Chaperones 2010;15:675–686.

B Dybdahl, S A Slørdahl, A Waage, P Kierulf, T Espevik, A Sundan, Myocardial ischaemia and the inflammatory response:release of heat shock protein 70 after myocardial infarction. cardiovascular medicine, Heart 2005;91:299–304.

Bialik S., Geenen D.L., Sasson I.E., Cheng R., Horner J.W., Evans S.M., 1997. Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently of p53. J Clin Invest 1997; 100:1363–1372.

Senturk T., Aydinlar A., Yilmaz Y., Yilmaztepe Oral A., Ozdabakoglu O. and Ulukaya E., 2009. Serial changes in circulating M30 antigen, a biomarker of apoptosis, in patients with acute coronary syndromes: relationship with the severity of coronary artery disease.Coronary Artery Disease 2009;20:494-498.