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

作者：Wang Yaoyong; Sawashita Jinko; Qian Jinze; Zhang Beiru; Fu Xiaoying; Tian Geng; Chen Lei; Mori Masayuki; Higuchi Keiichi^*

来源：The Journal of Lipid Research, 2011, 52(8): 1461-1470.

DOI：10.1194/jlr.M013235

• apolipoproteins
• cholesterol
• lipids
• distribution
• age
• amyloid heart disease

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.-Wang, Y., J. Sawashita, J. Qian, B. Zhang, X. Fu, G. Tian, L. Chen, M. Mori, and K. Higuchi. ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis. J. Lipid Res. 2011. 52: 1461-1470.

• 出版日期2011-8