P53+/− mice are protected against the pro‐atherosclerotic environment induced by a 12‐week Western diet

P53 controls metabolic pathways and oxidative stress levels. We therefore hypothesized that p53 regulates vascular homeostasis. To test this hypothesis we evaluated the systemic and vascular effects of a 12‐week pro‐oxidative Western diet (WD) beginning at 3 months of age in control (WT) and p53+\− mice (n=6). In WT mice, pro‐atherosclerotic plasmatic keratinocyte‐derived chemokine (103±30ng/L) and LDL cholesterol (0.6±0.1mM) levels increased two folds (p<0.05) following the WD (respectively 245±44ng/L and 1.3±0.1mM), while in p53+/− mice (107±35ng/L; 0.8±0.1mM) no significant changes occurred with the WD, suggesting a better adaptation of p53+/− mice to the pro‐atherogenic environment generated by the WD. Vascular oxidative stress estimated in aortas revealed no difference between WT and p53+\‐. Interestingly, superoxide dismutase activity was higher (160%, p<0.05) following the WD only in WT. These results suggest that WT mice need to upregulate vascular antioxidant defense to prevent deleterious effects induced by the WD, while endogenous lower levels of p53 prevent the rise of circulating atherosclerosis markers in mice following a WD. Supported by CIHR (MOP14406).