ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis[S]

• Published in: Journal of lipid research Vol. 52; no. 8; pp. 1461 - 1470
• Main Authors: Wang, Yaoyong, Sawashita, Jinko, Qian, Jinze, Zhang, Beiru, Fu, Xiaoying, Tian, Geng, Chen, Lei, Mori, Masayuki, Higuchi, Keiichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2011; The American Society for Biochemistry and Molecular Biology; Elsevier
• Subjects: age; Aging; Amyloid - biosynthesis; amyloid heart disease; Amyloidosis - metabolism; Amyloidosis - pathology; Amyloidosis - physiopathology; Animals; Apolipoprotein A-I - deficiency; Apolipoprotein A-I - genetics; Apolipoprotein A-II - blood; Apolipoprotein A-II - genetics; apolipoproteins; cholesterol; Cholesterol, HDL - blood; distribution; Female; Gene Deletion; lipids; Liver - chemistry; Liver - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium - chemistry; Myocardium - metabolism; Particle Size; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Triglycerides - blood; cholesterol; apolipoproteins; lipids; amyloid heart disease; distribution; age
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1194/jlr.M013235

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.