Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice.
Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice.
复制标题
DOI：
--
复制
发表时间：
1997-08
影响因子：
6.5
通讯作者：
N. Webb;M. C. D. Beer;D. Westhuyzen;M. Kindy;C. Banka;K. Tsukamoto;D. Rader;F. D. Beer
中科院分区：
文献类型：
--
作者：
N. Webb;M. C. D. Beer;D. Westhuyzen;M. Kindy;C. Banka;K. Tsukamoto;D. Rader;F. D. Beer
血清淀粉样蛋白A（SAA）是一种急性时相反应物，在严重炎症状态下可成为高密度脂蛋白（HDL）的主要载脂蛋白。然而，SAA的功能尚不清楚。为了研究SAA在缺乏载脂蛋白A-I的情况下形成HDL的能力，我们使用重组腺病毒在载脂蛋白A-I敲除（apoA-I（-/-））小鼠中表达小鼠SAA pI 6.15（CE/J）同种型。作为对照，apoA-I（-/-）小鼠注射表达人apoA-I的腺病毒。在没有任何内源性急性期SAA产生的情况下获得血浆SAA的高水平表达。SAA表达使血浆HDL胆固醇水平增加约2倍，但程度低于apoA-I表达（约10倍）。通过密度超离心从SAA表达小鼠中分离的HDL颗粒在大小和组成上是异质的，并且富含游离胆固醇以及apoE和apoA-IV。在血浆中表达的SAA中，只有一小部分（4%）与HDL颗粒相关，而apoA-I表达的SAA中有62%与HDL相关。我们的结论是SAA是无法取代apoA-I在HDL颗粒的形成。
Serum amyloid A (SAA) is an acute phase reactant that can become the predominant apolipoprotein of high density lipoprotein (HDL) during severe inflammatory states. However, the function of SAA is unknown. To study the ability of SAA to form HDL in the absence of apolipoprotein A-I, we expressed the mouse SAA pI 6.15 (CE/J) isoform in apolipoprotein A-I knock-out (apoA-I (-/-)) mice using a recombinant adenovirus. As a control, apoA-I (-/-) mice were injected with an adenovirus expressing human apoA-I. High level expression of plasma SAA was obtained in the absence of any endogenous acute phase SAA production. SAA expression increased plasma HDL cholesterol levels about 2-fold, but to a lesser extent than the expression of apoA-I (about 10-fold). The HDL particles isolated by density ultracentrifugation from SAA-expressing mice were heterogeneous in size and composition and rich in free cholesterol as well as apoE and apoA-IV. Of the SAA expressed in the plasma, only a small fraction (4%) was associated with HDL particles in contrast to expressed apoA-I, of which 62% was associated with HDL. We conclude that SAA is unable to substitute for apoA-I in HDL particle formation.