CD36 ABNORMALITY AND IMPAIRED MYOCARDIAL LONG-CHAIN FATTY-ACID UPTAKEIN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Some patients with hypertrophic cardiomyopathy (HCM) demonstrate abnor mal myocardial long-chain fatty acid (LCFA) metabolism. However, the e xact mechanism involved is unknown. Recently, it was proposed that myo cardial cells take up LCFAs via a specific mechanism, in which the CD3 6 molecule has been implicated as a possible candidate molecule. In ad dition, a high prevalence of CD36 deficiency was also found in a small number of HCM patients. Accordingly, the investigation of abnormality of the CD36 molecule in a large number of HCM patients may be useful in finding the possible cause of HCM. Moreover, the analysis of myocar dial LCFA uptake in patients with molecular abnormalities may be helpf ul in understanding the possible function of this molecule. In this st udy, in order to discover the relationship between HCM and the CD36 mo lecular abnormality, the expression level of platelet CD36 and CD36 cD NA in 55 HCM patients was analyzed, Twelve patients showed negligible (<5%) CD36 expression on their platelets. Among them, one was found to be homozygous for the C-478-->T substitution and 6 were heterozygous for the C-478-->T substitution. In 9 patients, CD36 was expressed by l ess than 50% of the platelets. One of them was found to be heterozygou s for the C-478-->T substi tution, Two other patients were also found to be heterozygous for this point mutation, although their platelets e xpressed CD36, Thus, 23 out of 55 (41.8%) HCM patients had negligible (<5%) or reduced (<50%) levels of CD36 expression on platelets, or had a point mutation of CD36 cDNA. These 55 HCM patients were also evalua ted with myocardial scintigraphy both for LCFA uptake and perfusion, w hich showed a moderate to severe discrepancy between myocardial LCFA a ccumulation and myocardial perfusion in 95.5% of the patients (21/23), On the other hand, 70% of the patients with normal (>90%) CD36 expres sion (14/20) did not show any severe discrepancies between myocardial LCFA accumulation and myocardial perfusion. These data could suggest t hat abnormal myocardial LCFA metabolism seen in HCM patients may be re lated to abnormality of the CD36 molecule, and that abnormalities of t his molecule may be linked to the cause of some types of HCM.