Expression of serum amyloid A protein in the absence of the acute phase response does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice.
Expression of serum amyloid A protein in the absence of the acute phase response does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice.
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发表时间：
1999-04
影响因子：
6.5
通讯作者：
Hiroshi Hosoai;N. Webb;Jane M. Glick;U. Tietge;Matthew S. Purdom;F. C. D. Beer;Daniel J. Rader
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文献类型：
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作者：
Hiroshi Hosoai;N. Webb;Jane M. Glick;U. Tietge;Matthew S. Purdom;F. C. D. Beer;Daniel J. Rader
高密度脂蛋白（HDL）胆固醇及其主要载脂蛋白（apo）A-I的血浆浓度在炎症状态下显著降低。血清淀粉样蛋白A（SAA）蛋白的血浆水平在急性期反应期间显著增加，并且在许多慢性炎症状态下升高。因为SAA与HDL相关，并且已经显示出能够在体外从HDL置换apoA-I，所以认为SAA的表达是炎症状态中HDL胆固醇和apoA-I降低的主要原因。为了直接检验这一假设，我们构建了表达鼠SAA和人SAA 1基因（两个物种中主要的急性期SAA蛋白）的重组腺病毒。将这些重组腺病毒静脉注射到野生型和人apoA-I转基因小鼠中，并将SAA表达对HDL胆固醇和apoA-I的影响与注射对照腺病毒的小鼠进行比较。SAA的血浆水平与小鼠和人的急性期反应中观察到的水平相当。然而，尽管小鼠或人SAA的血浆水平较高，但未观察到HDL胆固醇或apoA-I水平的显著变化。SAA被发现与HDL相关，但并没有特异性地改变胆固醇或人载脂蛋白A-I在脂蛋白中的分布。总之，在没有全身急性期反应的情况下，SAA的高血浆水平不会导致小鼠中HDL胆固醇或apoA-I的降低，这表明除了SAA表达之外，还有可能直接影响HDL代谢的急性期反应组分。
Plasma concentrations of high density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo)A-I are significantly decreased in inflammatory states. Plasma levels of the serum amyloid A (SAA) protein increase markedly during the acute phase response and are elevated in many chronic inflammatory states. Because SAA is associated with HDL and has been shown to be capable of displacing apoA-I from HDL in vitro, it is believed that expression of SAA is the primary cause of the reduced HDL cholesterol and apoA-I in inflammatory states. In order to directly test this hypothesis, we constructed recombinant adenoviruses expressing the murine SAA and human SAA1 genes (the major acute phase SAA proteins in both species). These recombinant adenoviruses were injected intravenously into wild-type and human apoA-I transgenic mice and the effects of SAA expression on HDL cholesterol and apoA-I were compared with mice injected with a control adenovirus. Plasma levels of SAA were comparable to those seen in the acute phase response in mice and humans. However, despite high plasma levels of murine or human SAA, no significant changes in HDL cholesterol or apoA-I levels were observed. SAA was found associated with HDL but did not specifically alter the cholesterol or human apoA-I distribution among lipoproteins. In summary, high plasma levels of SAA in the absence of a generalized acute phase response did not result in reduction of HDL cholesterol or apoA-I in mice, suggesting that there are components of the acute phase response other than SAA expression that may directly influence HDL metabolism.