title: ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis.
abstract: Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. ApoA-II has multiple physiological functions and can form senile amyloid fibrils (AApoAII) in mice. Most circulating apoA-II is present in lipoprotein A-I/A-II. To study the influence of apoA-I on apoA-II and AApoAII amyloidosis, apoA-I-deficient (C57BL/6J.Apoa1⁻/⁻) mice were used. Apoa1⁻/⁻ mice showed the expected significant reduction in total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride (TG) plasma levels. Unexpectedly, we found that apoA-I deficiency led to redistribution of apoA-II in HDL and an age-related increase in apoA-II levels, accompanied by larger HDL particle size and an age-related increase in TC, HDL-C, and TG. Aggravated AApoAII amyloidosis was induced in Apoa1⁻/⁻ mice systemically, especially in the heart. These results indicate that apoA-I plays key roles in maintaining apoA-II distribution and HDL particle size. Furthermore, apoA-II redistribution may be the main reason for aggravated AApoAII amyloidosis in Apoa1⁻/⁻ mice. These results may shed new light on the relationship between apoA-I and apoA-II as well as provide new information concerning amyloidosis mechanism and therapy.
authors.affiliation: Department of Aging Biology, Institute on Aging and Adaptation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.
authors.forename: Yaoyong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinko
authors.initials: J
authors.lastname: Sawashita
authors.forename: Jinze
authors.initials: J
authors.lastname: Qian
authors.forename: Beiru
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fu
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Masayuki
authors.initials: M
authors.lastname: Mori
authors.forename: Keiichi
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000375:Aging; D000682:Amyloid / Q000096:biosynthesis*; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D017353:Gene Deletion; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014280:Triglycerides / Q000097:blood
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D014280:Triglycerides