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rough the APOE-low density lipoprotein receptor (LDLR) pathway, and increasing cholesterol excretion into the bile, thereby reducing hepatic steatosis and aorta atherosclerosis in Western diet-fed mice. Our study reveals that high-level PON1 improved dysfunctional HDL and alleviated the development of atherosclerosis in mice. It is suggested that PON1 represents a promising target of HDL-based therapeutic strategy for HDL-related atherosclerotic cardiovascular disease. Our study reveals that high-level PON1 improved dysfunctional HDL and