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.
Highlights
Apolipoprotein A-II is the second major apolipoprotein following apolipoprotein A-I in HDL
To determine whether apolipoprotein A-I (apoA-I) deficiency influences the metabolism of Apolipoprotein A-II (apoA-II) and apoE, the major protein constituents of HDL from Apoa1Ϫ/Ϫ mice [7, 9], we determined the plasma levels of apoA-I, apoA-II, and apoE in two, four, and six-month-old WT and Apoa1Ϫ/Ϫ mice by Western blot analysis after separating plasma proteins by SDS-PAGE
The level of apoA-II decreased in two-month-old Apoa1Ϫ/Ϫ mice, there was a significant increase as Apoa1Ϫ/Ϫ mice aged (21.0 ± 6.0 and 31.1 ± 5.8 mg/dl at four and six months, respectively) (Fig. 1A, B)
Summary
Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. To study the influence of apoA-I on apoA-II and AApoAII amyloidosis, apoAI-deficient (C57BL/6J.Apoa1؊/؊) mice were used. 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. ApoA-II redistribution may be the main reason for aggravated AApoAII amyloidosis in Apoa1؊/؊ mice. ApoA-I deficiency in mice is associated with redistribution of apoA-II and aggravated AApoAII amyloidosis. This article is available online at http://www.jlr.org total HDL protein mass in humans Both apoA-I and apoA-II have important physiological functions in lipid transport and metabolism.
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