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Annals of Nuclear Medicine

, 12:261 | Cite as

Myocardial CD36 expression and fatty acid accumulation in patients with type I and II CD36 deficiency

  • Kenichi Watanabe
  • Yoshimi Ohta
  • Ken Toba
  • Yusuke Ogawa
  • Haruo Hanawa
  • Yoichi Hirokawa
  • Makoto Kodama
  • Naohito Tanabe
  • Satoru Hirono
  • Yuji Ohkura
  • Yuichi Nakamura
  • Kiminori Kato
  • Yoshifusa Aizawa
  • Ichiro Fuse
  • Seiichi Miyajima
  • Yoriko Kusano
  • Takafumi Nagamoto
  • Go Hasegawa
  • Makoto Naito
Original Article

Abstract

Long-chain fatty acids (LCFA) are one of the major cardiac energy substrates, so understanding LCFA metabolism may help in elucidating the mechanisms of various heart diseases. CD36 is a multifunctional membrane glycoprotein that acts not only as a receptor for thrombospondin, collagen and oxidized low density lipoprotein but also as a receptor for LCFA. We investigated the relationship between CD36 expression in myocardial capillary endothelial cells and myocardial LCFA uptake in patients with CD36 deficiency. We analyzed CD36 expression in blood cells from 250 patients with heart diseases by means of a flow cytometer. In 218 patients, myocardial LCFA scintigraphy was performed with123I-β-methyl-p-iodophenyl pentadecanoic acid (BMIPP). In 5 patients, myocardial capillary endothelial cells were examined immunohistochemically for CD36 expression. Eleven patients (4%) showed signs of type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Twenty patients (8%) had type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 11 patients with type I CD36 deficiency, no BMIPP accumulation was observed in the heart, but in 13 patients with type II CD36 deficiency, BMIPP accumulation in the heart was focally reduced, but there were no patients without BMIPP accumulation in the heart. Although the myocardial capillary endothelial cells from two CD36-positive patients expressed CD36, those from two patients with type I CD36 deficiency did not. In a patient with type II CD36 deficiency, some capillary endothelial cells displayed patchy CD36 expression.

CD36 deficiency was documented in 31 (12%) patients with heart diseases. Because CD36 was not expressed in the myocardial capillary endothelial cells in patients with type I CD36 deficiency, type I CD36 deficiency is closely related to lack of myocardial LCFA accumulation and metabolism in the myocardium.

Key words

CD36 deficiency fatty acid metabolism 123I-BMIPP heart disease cardiomyopathy 

References

  1. 1.
    Kudoh T, Tamaki N, Magata Y, Konishi J, Nohara R, Iwasaki A, et al. Metabolism substrate with negative myocardial uptake of Iodine-123-BMIPP.J Nucl Med 38: 548–553, 1997.PubMedGoogle Scholar
  2. 2.
    Tanaka T, Sohmiya, Kawamura K. Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy?J Mol Cell Cardiol 29: 121–127, 1997.CrossRefPubMedGoogle Scholar
  3. 3.
    Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA. CD36 is a receptor for oxidized low density lipoprotein.J Biol Chem 268: 11811–11816, 1993.PubMedGoogle Scholar
  4. 4.
    Yamamoto N, Akamatu N, Sakuraba H, Yamazaki H, Tanoue K. Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes.Blood 83: 392–397, 1994.PubMedGoogle Scholar
  5. 5.
    Kashiwagi H, Tomiyama Y, Honda S, Kosugi S, Shiraga M, Nagao N, et al. Molecular basis of CD36 deficiency —Evidence that a 478C-T substitution (proline 90-serine) in CD36 cDNA accounts for CD36 deficiency.J Clin Invest 95: 1040–1046, 1995.CrossRefPubMedGoogle Scholar
  6. 6.
    Nozaki S, Kashiwagi H, Yamashita S, Nakagawa T, Kostner B, Tomiyama Y, et al. Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36 deficient subjects.J Clin Invest 96: 1859–1865, 1995.CrossRefPubMedGoogle Scholar
  7. 7.
    Greenwalt DE, Scheck SH, Rhinehart-Jones T. Heart CD36 expression is increased in murine models of diabetes and in mice fed a high fat diet.J Clin Invest 96: 1382–1388, 1995.CrossRefPubMedGoogle Scholar
  8. 8.
    Watanabe K, Toba K, Ogawa Y, Aizawa Y, Tanabe N, Miyajima S, et al. Different patterns of123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency.KAKU IGAKU (Jpn J Nucl Med) 34: 1125–1130, 1997.Google Scholar
  9. 9.
    Watanabe K, Toba K, Ogawa Y, Kodama M, Hirono S, Ohkura Y, et al. Hypertrophic cardiomyopathy with type I CD36 deficiency.Jpn Circulation J 62: 541–542, 1998.CrossRefGoogle Scholar
  10. 10.
    Tamaki N, Kawamoto M, Yonekura Y, Fujibayashi Y, Takahashi N, Konishi J, et al. Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using branched fatty acid analog.J Nucl Med 33: 659–667, 1992.PubMedGoogle Scholar
  11. 11.
    Clark JB, Clark CMJ. The growth and metabolism of the developing heart.In: Jones CT, ed. Biochemical Development of the Fetus and Neonate. New York: Elsevier Biomedical Press, pp. 185–212, 1982.Google Scholar
  12. 12.
    Bremer J, Osmundsen H. Fatty acid oxidation and its regulation.In: Numa S, ed. Fatty Acid Metabolism and Its Regulation. New York: Elsevier Science Publishers, pp. 113–154, 1984.CrossRefGoogle Scholar
  13. 13.
    Stremmel W. Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process.J Clin Invest 81: 844–852, 1988.CrossRefPubMedGoogle Scholar
  14. 14.
    Schaffer JE, Lodish HF. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein.Cell 79: 427–436, 1994.CrossRefPubMedGoogle Scholar
  15. 15.
    Kusaka Y, Tanaka T, Okamoto F, Terasaki F, Matsunaga Y, Miyazaki H, et al. Effects of sulfo-N-succinimidyl palmitate on the rat heart: myocardial long-chain fatty acid uptake and cardiac hypertrophy.J Mol Cell Cardiol 27: 1605–1612, 1995.CrossRefPubMedGoogle Scholar
  16. 16.
    Kashiwagi H, Tomiyama Y, Kosugi S, Shiraga M, Lipsky R, Kanayama Y, et al. Identification of molecular defects in subject with type I CD36 deficiency.Blood 83: 3545–3552, 1994.PubMedGoogle Scholar
  17. 17.
    Huang MM, Bolen JB, Bamwall JW, Shattil SJ, Brugge JS. Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets.Proc Natl Sci USA 88: 7844–7848, 1991.CrossRefGoogle Scholar
  18. 18.
    Abumrad NA, El-Maghrabi MR, Amri EZ, Lopez E, Grimaldi PA. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation—Homology with human CD36.J Biol Chem 268: 17665–17668, 1993.PubMedGoogle Scholar
  19. 19.
    Tomiyama Y, Take H, Ikeda H, Mitani T, Furubayashi T, Mizutani H, et al. Identification of the platelet-specific alloantigen, Naka, on platelet membrane glycoprotein IV.Blood 75: 684–687, 1990.PubMedGoogle Scholar
  20. 20.
    Yamamoto N, Ikeda H, Tandon NN, Herman J, Tomiyama Y, Mitani T, et al. A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: naka platelets lack detectable GP IV (CD36).Blood 76: 1698–1703, 1990.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • Kenichi Watanabe
    • 1
  • Yoshimi Ohta
    • 1
  • Ken Toba
    • 2
  • Yusuke Ogawa
    • 2
  • Haruo Hanawa
    • 2
  • Yoichi Hirokawa
    • 2
  • Makoto Kodama
    • 2
  • Naohito Tanabe
    • 2
  • Satoru Hirono
    • 2
  • Yuji Ohkura
    • 2
  • Yuichi Nakamura
    • 2
  • Kiminori Kato
    • 2
  • Yoshifusa Aizawa
    • 2
  • Ichiro Fuse
    • 2
  • Seiichi Miyajima
    • 3
  • Yoriko Kusano
    • 3
  • Takafumi Nagamoto
    • 4
  • Go Hasegawa
    • 5
  • Makoto Naito
    • 5
  1. 1.Department of Clinical PharmacologyNiigata College of PharmacyNiigataJapan
  2. 2.First Department of MedicineNiigata University School of MedicineJapan
  3. 3.Division of CardiologyTsubame Rosai HospitalJapan
  4. 4.Department of PharmacologyNiigata College of PharmacyJapan
  5. 5.Second Department of PathologyNiigata University School of MedicineJapan

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