血清淀粉样蛋白 A3 具有促动脉粥样硬化作用。
Serum amyloid A3 is pro-atherogenic.
机构信息
Department of Veterans Affairs, Lexington, KY 40502, USA; Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
Department of Internal Medicine, University of Kentucky, Lexington, KY, 40536, USA; Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY, 40536, USA; Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, 40536, USA.
出版信息
Atherosclerosis. 2018 Jan;268:32-35. doi: 10.1016/j.atherosclerosis.2017.11.011. Epub 2017 Nov 17.
BACKGROUND AND AIMS
Serum amyloid A (SAA) predicts cardiovascular events. Overexpression of SAA increases atherosclerosis development; however, deficiency of two of the murine acute phase isoforms, SAA1.1 and SAA2.1, has no effect on atherosclerosis. SAA3 is a pseudogene in humans, but is an expressed acute phase isoform in mice. The goal of this study was to determine if SAA3 affects atherosclerosis in mice.
METHODS
ApoE mice were used as the model for all studies. SAA3 was overexpressed by an adeno-associated virus or suppressed using an anti-sense oligonucleotide approach.
RESULTS
Over-expression of SAA3 led to a 4-fold increase in atherosclerosis lesion area compared to control mice (p = 0.01). Suppression of SAA3 decreased atherosclerosis in mice genetically deficient in SAA1.1 and SAA2.1 (p < 0.0001).
CONCLUSIONS
SAA3 augments atherosclerosis in mice. Our results resolve a previous paradox in the literature and support extensive epidemiological data that SAA is pro-atherogenic.
背景和目的
血清淀粉样蛋白 A（SAA）可预测心血管事件。SAA 的过表达会增加动脉粥样硬化的发展；然而，两种鼠急性相同工型 SAA1.1 和 SAA2.1 的缺乏对动脉粥样硬化没有影响。SAA3 是人类的假基因，但在小鼠中是一种表达的急性相同工型。本研究的目的是确定 SAA3 是否会影响小鼠的动脉粥样硬化。
方法
载脂蛋白 E 小鼠被用作所有研究的模型。通过腺相关病毒过表达 SAA3 或使用反义寡核苷酸方法抑制 SAA3。
结果
与对照组相比，SAA3 的过表达导致动脉粥样硬化病变面积增加了 4 倍（p = 0.01）。抑制 SAA3 减少了在 SAA1.1 和 SAA2.1 基因缺失的小鼠中的动脉粥样硬化（p < 0.0001）。
结论
SAA3 增强了小鼠的动脉粥样硬化。我们的结果解决了文献中的一个先前的悖论，并支持了广泛的流行病学数据，即 SAA 具有促动脉粥样硬化作用。
Zotero 插件