LOX-1 genotype, dietary fat intake, and aerobic exercise training: Influence on endothelial function, oxidative stress, lipoprotein-lipids, and soluble LOX-1

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The lectin-like oxidized LDL receptor (LOX-1) is the major receptor for oxidized LDL (ox-LDL) in endothelial cells and plays a major role in the initiation and progression of atherosclerosis. Ox-LDL via LOX-1 causes endothelial activation and injury, induces lipid peroxidation, and alters inflammatory gene expression, and variation in the LOX-1 gene has been associated with cardiovascular disease risk. In addition, a soluble form of LOX-1 has been identified in plasma and may predict atherosclerotic disease progression. Thus, the purpose of this study was to investigate the effect of the LOX-1 3'UTR C/T and G501C polymorphisms on endothelial function, oxidative stress, plasma lipoprotein-lipids, and soluble LOX-1. The effect of these polymorphisms on the responses to dietary fat intake and aerobic exercise training was also examined. Forearm blood flow was measured using venous occlusion plethysmography at rest and during reactive hyperemia, and plasma levels of nitrates/nitrites, nitrotyrosine, ox-LDL, total antioxidant capacity, lipoprotein-lipids, and soluble LOX-1 were measured before and after six months of aerobic exercise training. The dietary ratio of polyunsaturated fat to saturated fat (P:S ratio) was determined using 7-day food records. The 3'UTR/CC and 501GC+CC groups had significantly higher baseline soluble LOX-1 levels than the CT/TT and GG groups, respectively. The G501C polymorphism was a significant predictor of baseline soluble LOX-1 levels, even after accounting for age, gender, race, BMI, and the 3'UTR polymorphism (p=0.024). There was a significant interaction between the 3'UTR polymorphism and dietary fat intake for plasma ox-LDL levels (p=0.011). At a high P:S ratio, the 3'UTR/CC group had significantly higher ox-LDL levels than the TT group (p=0.025). The opposite relationship was found at a low P:S ratio (p=0.044). The 3'UTR polymorphism also influenced changes in plasma TG levels with exercise training (p=0.036), while the G501C polymorphism influenced changes in soluble LOX-1 levels (p=0.012). In conclusion, variation in the LOX-1 gene does not appear to be associated with endothelial function, oxidative stress, or plasma lipid levels, but may influence changes in these variables in response to dietary fat intake and exercise training. Moreover, polymorphisms in LOX-1, especially the G501C polymorphism, may regulate circulating levels of soluble LOX-1.