CD36 genotype and long-chain fatty acid uptake in the heart.
Homozygous or compound heterozygous mutation of the CD36 gene (CD36-/-) in humans results in severe defects of the uptake of long-chain fatty acids (LCFAs) in the heart. Because the effect of a single mutation of this gene (CD36+/-) on the LCFA uptake is not known, it was evaluated in 29 subjects with the CD36 wild-type gene (WT) (6 healthy subjects, 10 patients with heart disease), CD36+/- (4 healthy subjects, 5 patients) and CD36-/- (4 patients). The CD36 genotype was identified in the coding region of genomic DNA, and the expression of CD36 protein was examined by flow cytometry after staining with monoclonal anti-CD36 antibody. The LCFA uptake in the heart was assessed as the radioactivity accumulation ratio of heart to mediastinum after intravenous administration of iodine-123 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (H/M ratio). The H/M ratios in WT, CD36+/- and CD36-/- were 2.28 +/- 0.10, 1.90 +/- 0.06 and 1.40 +/- 0.11, respectively (p < 0.0001, among groups). The H/M ratio between healthy subjects and patients with heart disease for WT and CD36+/- did not differ significantly (ie, those of WT and CD36+/- in healthy subjects and patients were 2.29 +/- 0.08 vs 2.27 +/- 0.12 and 1.90+/- 0.07 vs 1.89 +/- 0.05, respectively). Not only CD36-/- but also CD36+/- resulted in a significant reduction of the LCFA uptake in the heart independent of heart disease, suggesting genotype dependency and that CD36 might be a fundamental determinant of myocardial LCFA uptake.
Kintaka
Taigo
T
Department of Internal Medicine, Osaka Medical College,Takatsuki, Japan.
Tanaka
Takao
T
Imai
Makoto
M
Adachi
Itaru
I
Narabayashi
Isamu
I
Kitaura
Yasushi
Y
D000328:Adult; D000368:Aged; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006321:Heart / Q000000981:diagnostic imaging; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009206:Myocardium / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D018955:CD36 Antigens; D005227:Fatty Acids