Chronic infusion of salusin-α and -β exerts opposite effects on atherosclerotic lesion development in apolipoprotein E-deficient mice

被引：82
作者：
Nagashima, Masaharu [1 ]
Watanabe, Takuya [2 ]
Shiraishi, Yuji [1 ]
Morita, Ryou [1 ]
Terasaki, Michishige [1 ]
Arita, Shigeko [2 ]
Hongo, Shigeki [2 ]
Sato, Kengo [3 ]
Shichiri, Masayoshi [4 ]
Miyazaki, Akira [2 ]
Hirano, Tsutomu [1 ]
机构：
[1] Showa Univ, Sch Med, Div Diabet Metab & Endocrinol, Dept Med, Tokyo 1428666, Japan
[2] Showa Univ, Sch Med, Dept Biochem, Tokyo 1428555, Japan
[3] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Unit Clin Anat, Tokyo 1138519, Japan
[4] Kitasato Univ, Sch Med, Dept Diabet Endocrinol & Metab, Sagamihara, Kanagawa 2288555, Japan
来源：
ATHEROSCLEROSIS | 2010年 / 212卷 / 01期
基金：
日本学术振兴会;
关键词：
Salusins; Atherosclerosis; Macrophage; Foam cell formation; Oxidized LDL; FOAM CELL-FORMATION; EXPRESSION; SERUM;
D O I：
10.1016/j.atherosclerosis.2010.04.027
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Objective: Human salusin-alpha and -beta are two-related peptides processed from the same precursor, pre-prosalusin. Our previous in vitro studies have shown that human macrophage foam cell formation is stimulated by salusin-beta but suppressed by salusin-alpha. Thus we investigated the effects of salusin-alpha and -beta on atherosclerotic plaque formation in vivo in apolipoprotein E-deficient (ApoE-/-) mice. Methods: Saline (vehicle), salusin-alpha or -beta (0.6 nmol/kg/h) was continuously infused through osmotic mini-pumps into 13-week-old ApoE-/- mice for 8 weeks. Aortic atherosclerosis, oxidized LDL-induced cholesterol ester accumulation (foam cell formation), and its related gene expression in exudate peritoneal macrophages were determined. Results: After 4-week infusion of salusin-beta, atherosclerotic lesions were 2.6 times greater than vehicle controls, which paralleled 1.9-fold increase in foam cell formation and up-regulation of scavenger receptors (CD36, scavenger receptor class A) and acyl-CoA: cholesterol acyltransferase-1(ACAT1). In contrast, salusin-alpha decreased serum total cholesterol levels by 15% and foam cell formation by 68% associated with ACAT1 down-regulation. After 8-week infusion of salusin-alpha, atherosclerotic lesions were significantly suppressed by 54% compared with vehicle controls. Conclusions: Our study provided the first evidence that salusin-beta accelerates the development of atherosclerotic lesions associated with up-regulation of scavenger receptors and ACAT1 in ApoE(-/-) mice. Whilst, salusin-alpha exerts anti-atherosclerotic effects by suppressing serum total cholesterol levels and ACAT1 expression. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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收藏
页码：70 / 77
页数：8
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