title: Impact of age and sex on the development of atherosclerosis and expression of the related genes in apoE deficient mice.
abstract: Development of atherosclerosis is a chronic pathological process. ApoE deficient (apoE(-/-)) mice spontaneously develop atherosclerotic lesions. However, the impact of age and sex on lesions and expression of the related genes have not been fully elucidated. In this study, we collected blood and tissue samples from normal chow fed male and female apoE(-/-) mice at different ages, and determined serum lipids, PCSK9 levels, en face aortic lesions and expression of some pro- or anti-atherogenic genes. We determined that lesion development was clearly associated with age, and more lesions in males than females (12.6 ± 1.7% vs. 8.9 ± 1.1% at 8 months old, P < 0.05). Associated with age, serum total, LDL- and HDL-cholesterol and PCSK9 levels increased with more PCSK9 in females than males (313 ± 31 ng/mL vs. 239 ± 28 ng/mL at 8 months old, P < 0.05); expression of liver LDLR and ABCA1 decreased while of SR-BI increased; expression of macrophage ABCA1 and SR-BI decreased but of CD36 increased. Estrogen and tamoxifen induced ABCA1 and SR-BI expression, respectively, in macrophages isolated from female mice at the different age. Taken together, our study suggests that aging facilitates lesion development in apoE(-/-) mice with greater effect on male mice. The lesion development is also related to expression of pro- or anti-atherogenic genes in tissues, particularly in macrophages.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Medical Engineering, Hefei University of Technology, Hefei, China; College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Biotherapy, Nankai University, Tianjin, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Han
authors.affiliation: College of Medical Engineering, Hefei University of Technology, Hefei, China; School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Biotherapy, Nankai University, Tianjin, China. Electronic address: yuanli2014@nankai.edu.cn.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Medical Engineering, Hefei University of Technology, Hefei, China; College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Biotherapy, Nankai University, Tianjin, China. Electronic address: yajunduan@nankai.edu.cn.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Duan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism*; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D018955:CD36 Antigens / Q000378:metabolism*; D005260:Female; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012727:Sex Characteristics
chemical_list: D064286:ATP Binding Cassette Transporter 1; D001057:Apolipoproteins E; D018955:CD36 Antigens; D008055:Lipids; C577833:Abca1 protein, mouse
keywords: ABCA1; Age; Atherosclerosis; CD36; Sex