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

Citation
S. Nozaki 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 C BIOCH, 192(1-2), 1999, pp. 129-135
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR AND CELLULAR BIOCHEMISTRY
ISSN journal
0300-8177 → ACNP
Volume
192
Issue
1-2
Year of publication
1999
Pages
129 - 135
Database
ISI
SICI code
0300-8177(199902)192:1-2<129:CMLFAT>2.0.ZU;2-L
Abstract
Long-chain fatty acids (LCFA) are the major energy substrate for heart and their oxidation is important for achieving maximal cardiac work. However, t he mechanism of uptake of LCFA by myocardium has not been clarified. We pre viously reported that bovine myocardial LCFA transporter has a sequence hom ology to human CD36. Clinically, total defect of myocardial uptake of radio labeled long-chain fatty acid analog [I-123-BMIPP: Iodine-123 15-(p-iodophe nyl)-(R,S)-methylpentadecanoic acid] has been reported in some restricted c ases, but the etiology has not been clarified. In the present study, we ana lyzed CD36 expression and CD36 gene in subjects who showed total lack of my ocardial I-123-BMIPP accumulation, and, vice versa, evaluated myocardial '2 jI-BMIPP uptake in subjects with CD36 deficiency. Four unrelated subjects w ere evaluated; Two were found to have negative myocardial LCFA accumulation by I-123-BMIPP scintigraphy, after which the expression of CD36 on their p latelets and monocytes was analyzed. Remaining two subjects were identified as CD36 deficiency by screening, then I-123-BMIPP scintigraphy was perform ed. Expression of CD36 on platelets and monocytes was measured by flow cyto metric analysis. The molecular defects responsible for CD36 deficiency was detected by allele-specific restriction enzyme analysis. CD36 expression wa s totally deficient in all 4 subjects on both platelets and monocytes. Two subjects were homozygous for a C-478-->T mutation. One was heterozygous for the dinucleotide deletion of exon V and single nucleotide insertion of exo n X, and remaining one was considered to be heterozygous for the dinucleoti de deletion of exon V and an unknown gene abnormality. All cases demonstrat ed a completely negative accumulation of myocardial LCFA despite of normal myocardial perfusion, which was evaluated by thallium scintigraphy. In addi tion, all cases demonstrated apparently normal hepatic LCFA accumulation Th us, these findings suggested that CD36 acts as a major myocardial specific LCFA transporter in humans.