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CD36 mediates long-chain fatty acid transport in human myocardium: Complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency

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Abstract

Long-chain fatty acids (LCFA) are the major energy substrate for heart and their oxidation is important for achieving maximal cardiac work. However, the mechanism of uptake of LCFA by myocardium has not been clarified. We previously reported that bovine myocardial LCFA transporter has a sequence homology to human CD36. Clinically, total defect of myocardial uptake of radiolabeled long-chain fatty acid analog [123I-BMIPP: Iodine-123 15-(p-iodophenyl)-(R,S)-methylpentadecanoic acid] has been reported in some restricted cases, but the etiology has not been clarified. In the present study, we analyzed CD36 expression and CD36 gene in subjects who showed total lack of myocardial 123I-BMIPP accumulation, and, vice versa, evaluated myocardial 123I-BMIPP uptake in subjects with CD36 deficiency. Four unrelated subjects were evaluated; Two were found to have negative myocardial LCFA accumulation by 123I-BMIPP scintigraphy, after which the expression of CD36 on their platelets and monocytes was analyzed. Remaining two subjects were identified as CD36 deficiency by screening, then 123I-BMIPP scintigraphy was performed. Expression of CD36 on platelets and monocytes was measured by flow cytometric analysis. The molecular defects responsible for CD36 deficiency was detected by allele-specific restriction enzyme analysis. CD36 expression was totally deficient in all 4 subjects on both platelets and monocytes. Two subjects were homozygous for a 478C→T mutation. One was heterozygous for the dinucleotide deletion of exon V and single nucleotide insertion of exon X, and remaining one was considered to be heterozygous for the dinucleotide deletion of exon V and an unknown gene abnormality. All cases demonstrated a completely negative accumulation of myocardial LCFA despite of normal myocardial perfusion, which was evaluated by thallium scintigraphy. In addition, all cases demonstrated apparently normal hepatic LCFA accumulation Thus, these findings suggested that CD36 acts as a major myocardial specific LCFA transporter in humans.

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Authors and Affiliations

  1. The Second Department of Internal Medicine, Osaka University Medical School, Osaka, Japan

    Shuichi Nozaki, Shizuya Yamashita, Koichi Sohmiya, Atsuyuki Nakata, Tsutomu Nakagawa, Kengo Matsumoto, Kaoru Kameda-Takemura, Seiji Tadekoro, Yoshiaki Tomiyama & Yuji Matsuzawa

  2. The Third Division, Department of Internal Medicine, Osaka Medical College, Osaka, Japan

    Takao Tanaka, Fumio Okamoto, Yasushi Kitaura & Keishiro Kawamura

  3. Minoo City Hospital, Osaka, Japan

    Tohru Yoshizumi

  4. Saiseikai Nakatsu Hospital, Osaka, Japan

    Chikao Kotake & Hiroyuki Nishida

  5. Department of Blood Transfusion, Osaka University Hospital, Osaka, Japan

    Yoshiyuki Kurata

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  1. Shuichi Nozaki
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  2. Takao Tanaka
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Nozaki, S., Tanaka, T., Yamashita, S. et al. CD36 mediates long-chain fatty acid transport in human myocardium: Complete myocardial accumulation defect of radiolabeled long-chain fatty acid analog in subjects with CD36 deficiency. Mol Cell Biochem 192, 129–135 (1999). https://doi.org/10.1023/A:1006816702425

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