Effect of a chronic cholesterol-rich diet on vascular structure and oxidative stress in LDLR-/- mice

There is conflicting evidence regarding the relationship between hypercholesterolemia and oxidative stress in vessels. To test the potential relationship, a mouse model of hypercholesterolemia was used.

Low density lipoprotein receptor-deficient (LDLR(-/-)) and control (C57Bl/6) mice were fed a normal or (1.25%) high-cholesterol (HC) diet for 8 weeks, and the incidence of this chronic diet was evaluated on the degree of vascular oxidative stress and vascular structure (collagen content and lipid infiltration expressed in arbitrary units: AU=%/mm(2)).

Animals treated with the HC diet presented an increase in lipid infiltration (0.35±0.13 vs. 1.7±0.18 control and 1.04±0.16 vs. 1.84±0.23 LDLR(-/-), AU p<0.05) associated with higher collagen content (control: 2.13±0.40 vs. 3.46±0.36 and LDLR(-/-): 2.37±0.36 vs. 3.79±0.60; AU p<0.05 red Sirius staining). Interestingly, ROS production in the aorta was only increased in the LDLR(-/-) +cholesterol group (0.17±0.04 and 0.16±0.05 in the control groups, 0.14±0.02 vs. 0.34±0.06 in the LDLR(-/-) groups, p<0.05). C57Bl/6 and LDLR(-/-) mice presented altered vascular structure associated with the rich cholesterol diet, which was not necessarily associated with increased oxidative stress.

These findings highlight the complex interrelation between oxidative stress and lipid metabolism in the circulatory tract.