Abstract
Cytoplasmic heart-type fatty acid-binding protein (H-FABPc) is a low molecular weight protein with abundant presence in the myocardium. Upon ischemia it is released from the heart and can subsequently be detected in plasma and urine. In this study, the value of measurement of H-FABPc excreted into urine for the diagnosis of myocardial infarction (MI) is investigated in the rat. To this end, firstly the kinetic behaviour of H-FABPc in plasma was examined and its release into urine quantified.
After injection of purified H-FABPc in normal animals, a net recovery in urine of 14–29% was found. The kinetic behaviour of H-FABPc in plasma was characterized by a total clearance of 0.33 ml/min and a half-life value of total elimination of about 270 min.
Knowing these plasma characteristics of H-FABPc, a comparison was made between the cumulative amounts of H-FABPc released in the 24-hour urine of MI rats and of sham-operated animals. In MI rats, with a mean morphometric MI size of 43%, the mean total amount of H-FABPc excreted into urine was 79 μg, while in sham-operated rats this was 23 μg. This difference between both groups is significant (p<0.001)
It is concluded that urinary H-FABPc can be used as a noninvasive marker for MI in the rat.
Similar content being viewed by others
References
Ockner RK, Manning JA, Poppenhausen RB, Ho WKL: A binding protein for fatty acids in cytosol in intestinal mucosa, liver, myocardium, and other tissues. Science 177:56–58, 1972
Bass NM: The cellular fatty acid binding proteins: Aspects of structure, regulation and function. Int Rev Cytol 111:143–184, 1988
Glatz JFC, Van Der Vusse GJ: Cellular fatty acid-binding proteins: Current concepts and future directions. Mol Cell Biochem 98:237–251, 1990
Sacchettini JC, Said B, Schulz H, Gordon JI: Rat heart fatty acid-binding protein is highly homologous to the murine adipocyte 422 protein and the P2 protein of peripheral nerve myelin. J Biol Chem 261:8218–8223, 1986
Heuckeroth RO, Birkenmeier EH, Levin MS, Gordon JI: Analysis of the tissue-specific expression, developmental regulation, and linkage relationships of a rodent gene encoding heart fatty acid-binding protein. J Biol Chem 262:9709–9717, 1987
Paulussen RJA, Geelen MJH, Beynen AC, Veerkamp JH: Immunochemical quantitation of fatty-acid-binding proteins. I. Tissue and intracellular distribution, postnatal development and influence of physiological conditions on rat heart and liver FABP. Biochim Biophys Acta 1001:201–209, 1989
Watanabe M, Ono T, Kondo H: Immunohistochemical studies on the localisation and ontogeny of heart fatty acid binding protein in the rat. J Anat 174:81–95, 1991
Vork MM, Glatz JFC, Surtel DAM, Knubben HJM, Van Der Vusse GJ: A sandwich enzyme linked immuno-sorbent assay for the determination of rat heart fatty acid-binding protein using the streptavidin-biotin system. Application to tissue and effluent samples from normoxic rat heart perfusion. Biochim Biophys Acta 1075:199–205, 1991
Glatz JFC, Van Bilsen M, Paulussen RJA, Veerkamp JH, Van DerVusse GJ, Reneman RS: Release of fatty acid-binding protein from the isolated rat heart subjected to ischemia and reperfusion or to the calcium paradox. Biochim Biophys Acta 961:148–152, 1988
Knowlton AA, Apstein CS, Saouf R, Brecher P: Leakage of heart fatty acid binding protein with ischemia and reperfusion in the rat. J Mol Cell Cardiol 21:577–583, 1989
Tanaka T, Hirota Y, Sohmiya K-I, Nishimura S, Kawamura K: Serum and urinary human heart fatty acid-binding protein in acute myocardial infarction. Clin Biochem 24:195–201, 1991
Kleine AH, Glatz JFC, Van Nieuwenhoven FA, Van Der Vusse GJ: Release of heart fatty acid-binding protein into plasma after acute myocardial infarction in man. Mol Cell Biochem 116:155–162, 1992
Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E: Myocardial infarct size and ventricular function in rats. Circ Res 44:503–512, 1979
Schoemaker RG, Debets JJM, Struyker Boudier HAJ, Smits JFM: Beneficial hemodynamic effects of two weeks' milrinone treatment in conscious rats with heart failure. Eur J Pharmacol 182: 527–535, 1990
De Vries PJF, Tyssen CM, Struyker Boudier HAJ, Smits JFM: Physiological role of ANP under resting and volume expanded conditions in normotensive rats. Life Sci 47:2291–2297, 1990
Van Nieuwenhoven FA, Vork MM, Surtel DAM, Kleine AH, Van DerVusse GJ, Glatz JFC: High-yield two-step chromatographic procedure for purification of fatty acid-binding protein from human heart. J Chromatogr 570:173–179, 1991
Vork MM, Glatz JFC, Surtel DAM, Van Der Vusse GJ: Assay of the binding of fatty acids by proteins: Evaluation of the Lipidex 1000 procedure. Mol Cell Biochem 98:111–117, 1990
Van Krimpen C, Smits JFM, Cleutjens JPM, Debets JJM, Schoemaker RG, Struyker Boudier HAJ, Bosman FT, Daemen MJAP: DNA synthesis in the non-infarcted cardiac interstitium after left coronary artery ligation in the rat: Effects of captopril. J Mol Cell Cardiol 23:1245–1253, 1991
Pfeffer MA, Pfeffer JM, Steinberg C, Finn P: Survival after an experimental myocardial infarction: Beneficial effects of longterm therapy with captopril. Circulation 72:406–412, 1985
Cairns JA, Missirlis E, Walker WHC: Usefulness of serial determinations of myoglobin and creatine kinase in serum compared for assessment of acute myocardial infarction. Clin Chem 29:469–473, 1983
Adams EC, Elliott TA: Urinary myoglobin in myocardial infarction. JAMA 211:1013–1014, 1970
Saranchak HJ, Bernstein SH: A new diagnostic test for acute myocardial infarction. The detection of myoglobinuria by radioimmunodiffusion assay. JAMA 228:1251–1255, 1974
Kagen L, Scheidt S, Roberts L, Porter A, Paul H: Myoglobinemia following acute myocardial infarction. Am J Med 58:177–182, 1975
Stone MJ, Waterman MR, Harimoto D, Murray G, Wilson N, Platt MR, Blomqvist G, Willerson JT: Serum myoglobin level as diagnostic test in patients with acute myocardial infarction. Br Heart J 39:375–380, 1977
Sylvén C, Jansson E, Böör K: Myoglobin content in human skeletal muscle and myocardium: Relation to fibre size and oxidative capacity. Cardiovasc Res 18:443–446, 1984
Paulussen RJA, Van Moerkerk HTB, Veerkamp JH: Immunochemical quantitation of fatty acid-binding proteins. Tissue distribution of liver and heart FABP types in human and porcine tissues. Int J Biochem 22:393–398, 1990
Klocke FJ, Copley DP, Krawczyk JA, Reichlin M: Rapid renal clearance of immunoreactive canine plasma myoglobin. Circulation 65:1522–1528, 1982
Righetti PG, Caravaggio T: Isoelectric points and molecular weights of proteins. A table. J Chromatogr 127:1–28, 1976
Fournier N, Geoffroy M, Deshusses J: Purification and characterization of a long chain, fatty-acid-binding protein supplying the mitochondrial β-oxidative system in the heart. Biochim Biophys Acta 533:457–464, 1978
Vork MM, Trigault N, Snoeckx LHEH, Glatz JFC, Van Der Vusse GJ: Heterogeneous distribution of fatty acid-binding protein in the hearts of Wistar Kyoto and spontaneously hypertensive rats. J Mol Cell Cardiol 24:317–321, 1992
Glatz JFC, Vork MM, Cistola DP, Van Der Vusse GJ: Cytoplasmic fatty acid-binding protein: Significance for intracellular transport of fatty acids and putative role in signal transduction pathways. Prostaglandins, Leukotrienes and Essential Fatty Acids 48:33–41, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Volders, P.G.A., Vork, M.M., Glatz, J.F.C. et al. Fatty acid-binding proteinuria diagnoses myocardial infarction in the rat. Mol Cell Biochem 123, 185–190 (1993). https://doi.org/10.1007/BF01076491
Issue Date:
DOI: https://doi.org/10.1007/BF01076491