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
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
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.