hyperlipidemia and atherosclerotic lesion development in ldlr-deficient mice on a long-term high-fat diet高脂血症和动脉粥样硬化病变发展ldlr-deficient小鼠长期高脂肪的饮食.pdfVIP

Hyperlipidemia and Atherosclerotic Lesion Development in Ldlr-Deficient Mice on a Long-Term High-Fat Diet 1 1 1 2 1 1 1 Yanling Ma , Wenyi Wang , Jie Zhang , Youli Lu , Wenyu Wu , Hong Yan , Yiping Wang * 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China, 2 Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China Abstract Background: Mice deficient in the LDL receptor (Ldlr2/ 2 mice) have been widely used as a model to mimic human atherosclerosis. However, the time-course of atherosclerotic lesion development and distribution of lesions at specific time- points are yet to be established. The current study sought to determine the progression and distribution of lesions in Ldlr2/ 2 mice. Methodology/Principal Findings: Ldlr-deficient mice fed regular chow or a high-fat (HF) diet for 0.5 to 12 months were analyzed for atherosclerotic lesions with en face and cross-sectional imaging. Mice displayed significant individual differences in lesion development when fed a chow diet, whereas those on a HF diet developed lesions in a time-dependent and site-selective manner. Specifically, mice subjected to the HF diet showed slight atherosclerotic lesions distributed exclusively in the aortic roots or innominate artery before 3 months. Lesions extended to the thoracic aorta at 6 months and abdominal aorta at 9 months. Cross-sectional analysis revealed the presence of advanced lesions in the aortic sinus after 3 months in the group on the HF diet and in the innominate artery at 6 to 9 months. The HF diet additionally resulted in increased total cholesterol, LDL, glucose, and HBA1c levels, along with