Abstract 1366: Serum Concentrations of Linoleic Acids and Their Derivatives by Lipid Peroxidation Are Increased in Patients With CD36 Deficiency
Background: CD36, a class B scavenger receptor, is one of the transporters of long-chain fatty acids. In patients with CD36 deficiency (CD36-D), serum free fatty acid (FFA) level is significantly higher during fasting and postprandial state (Masuda et al., J. Lipid Res. 2009). Moreover, patients with CD36-D are frequently associated with multiple risk factors and insulin resistance, and they suffer from severe atherosclerotic cardiovascular diseases. Although implications of high FFA level in terms of atherogenesis has not been elucidated clearly, it was shown that high levels of total FFA and linoleic acid were strongly correlated with the increase of oxidative stress and high levels of lipid peroxidation derivatives of arachidonic acids, hydroxyeicosatetraenoic acids (HETE) impaired the vasodilator effects of NO and promoted atherosclerotic lesions. In this study, we investigated which kinds of FFA are increased and whether FFA peroxidation derivatives are increased or not in patients with CD36-D.
Methods and Results: Levels of total FFA, FFA profiles and levels of arachidonic acid derivatives (total HETE and 8-iso-PGF2α) and linoleic acid derivatives (hydroxyoctadecadienoic acids, HODE) were measured in patients with CD36-D (n=4) and healthy subjects (n=12) during fasting state. Levels of total FFA and linoleic acids were significantly higher in CD36-D patients compared with control subjects (patients vs healthy subjects, total FFA; 3920±1323 vs 2221±487 μg/ml, p<0.05, linoleic acid; 791±102 vs 593±136, p<0.05). Although there was no significant difference in 8-iso-PGF2α levels, total HETE and HODE levels were significantly higher in patients (total HETE; 883±178 vs 479±347 nM, p<0.01, total HODE; 932±86 vs 459±328 nM, p<0.0005).
Conclusion: These results suggest that the increase in linoleic acids and FFA derivatives by lipid peroxidation (HODE and HETE) might be one of the causes of increased atherogenicity in patients with CD36-D through enhancing oxidative stress.