Conclusions
Genetic disruption of MRP1 appears to reduce blood pressure and vascular oxidative stress in vivo, which leads to improved endothelial function and a reduced plaque burden in atherosclerotic mice. Therefore, MRP1 might represent a promising therapeutic target to improve endothelial function in patients suffering from atherosclerosis.
Material and methods
MRP1-/- LDLr-/- double knockout mice. were fed a high-fat and cholesterol-rich diet for 7 weeks. Thereafter, endothelial function was assessed in isolated aortic rings. Reactive oxygen species were quantified by L-012 chemiluminescence, and the atherosclerotic plaque burden was measured following oil red O staining.
Methods
MRP1-/- LDLr-/- double knockout mice. were fed a high-fat and cholesterol-rich diet for 7 weeks. Thereafter, endothelial function was assessed in isolated aortic rings. Reactive oxygen species were quantified by L-012 chemiluminescence, and the atherosclerotic plaque burden was measured following oil red O staining.
Results
Endothelium-dependent vasodilation of MRP1-/- LDLr-/- double knockout mice was significantly improved compared to MRP1-competent LDLr-/- single knockout mice (0.56 ±0.06 vs. 0.78 ±0.08; n = 10; p = 0.048). This improvement was accompanied by a significant reduction in reactive oxygen species formation within the aortic tissue (102 ±27 RLU/s/mg vs. 315 ±78 RLU/s/mg, n = 9-11, p = 0.03). Moreover, the atherosclerotic plaque burden of MRP1-/- LDLr-/- double knockout mice was significantly reduced (0.06 ±0.01 vs. 0.12 ±0.02; n = 6; p = 0.047). Finally, arterial blood pressure was significantly reduced in MRP1-/- LDLr-/- double knockout mice (93 ±5 mm Hg vs. 128 ±4 mm Hg; n = 8-12; p < 0.001). Conclusions: Genetic disruption of MRP1 appears to reduce blood pressure and vascular oxidative stress in vivo, which leads to improved endothelial function and a reduced plaque burden in atherosclerotic mice. Therefore, MRP1 might represent a promising therapeutic target to improve endothelial function in patients suffering from atherosclerosis.