Aims: 

LOX-1 is a major vascular receptor for oxidized low-density lipoprotein (oxLDL). In this study, we analyzed the impact of LOX-1 overexpression and high dietary fat intake on vascular function in small resistance arteries.

Methods and Results: 

Relaxation of mesenteric arteries was measured using a wire myograph. Compared with control group, mice overexpressing LOX-1 on high-fat diet (FD) had preserved vascular smooth muscle relaxation, but impaired endothelium-dependent relaxation via NO. Vascular NO availability was decreased by exaggerated formation of reactive oxygen species and decreased endothelial NO synthase expression. Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation via cytochrome P450 metabolites was increased in LOX-1+FD animals, but did not completely compensate for the loss of NO. Currents of calcium-activated potassium channels with large conductance (BK_Ca channels) were measured by voltage-clamp method. The BK_Ca current amplitudes were not altered in endothelial cells, but highly increased in vascular smooth muscle cells from resistance arteries of LOX-1 overexpressing mice on FD. BK_Ca currents were activated by low dose H₂O₂ and cytochrome P450 metabolites 11,12-EET and 14,15-EET as EDHF in control mice.

Conclusion: 

LOX-1 overexpression and FD caused functional changes in endothelial and vascular smooth muscle cells of small resistance arteries.