Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner
Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner
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DOI：
10.2353/ajpath.2008.080201
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发表时间：
2008-12-01
影响因子：
6
通讯作者：
Tannock, Lisa R.
中科院分区：
文献类型：
--
作者：
Wilson, Patricia G.;Thompson, Joel C.;Tannock, Lisa R.
炎症标志物血清淀粉样蛋白A(SAA)和C反应蛋白(CRP)是心脏病的预测指标，并被认为在动脉粥样硬化的发展中起着因果作用，而在动脉粥样硬化中，蛋白多糖对脂蛋白的滞留是至关重要的。本研究的目的是确定SAA和/或CRP是否以促进动脉粥样硬化的方式改变血管蛋白多糖的合成和脂蛋白滞留。用SAA或C反应蛋白(1~100 mg/L)刺激血管平滑肌细胞，分离并鉴定原糖链。SAA，而不是CRP，以剂量依赖的方式使蛋白多糖硫酸盐掺入增加50%至100%(P<；0.0001)，增加糖胺多糖链长度，并增加低密度脂蛋白结合亲和力(K-d，与对照蛋白多糖相比，SAA组为29mU g/mlLDLvs 90mU g/mlLDLs；P<；0.005)。此外，SAA通过诱导内源性转化生长因子-β上调Biglycan的表达。为了确定SAA是否刺激体内蛋白合成，ApoE(-/-)小鼠被注射了表达人SAA-1、空病毒或生理盐水的腺病毒。与接受空病毒或生理盐水的小鼠相比，接受表达SAA的腺病毒的小鼠血浆中的转化生长因子-β浓度增加，主动脉双聚糖含量增加。因此，SAA通过刺激转化生长因子-β以促动脉粥样硬化的方式改变血管蛋白多糖，并可能在动脉粥样硬化的发展中发挥因果作用。(Am J Pathol2008173：1902-1910；DOI：10.2353/ajpath.2008.080201)
Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are predictive of cardiac disease and are proposed to play causal roles in the development of atherosclerosis, in which the retention of lipoproteins by vascular wall proteoglycans is critical. The purpose of this study was to determine whether SAA and/or CRP alters vascular proteoglycan synthesis and lipoprotein retention in a pro-atherogenic manner. Vascular smooth muscle cells were stimulated with either SAA or CRP (1 to 100 mg/L) and protcoglycans were then isolated and characterized. SAA, but not CRP, increased proteoglycan sulfate incorporation by 50 to 100% in a dose-dependent manner (P < 0.0001), increased glycosaminoglycan chain length, and increased low-density lipoprotein (LDL) binding affinity (K-d, 29 mu g/ml LDL versus 90 mu g/ml LDL for SAA versus control proteoglycans; P < 0.005). Furthermore, SAA up-regulated biglycan via the induction of endogenous transforming growth factor (TGF)-beta. To determine whether SAA stimulated proteoglyean synthesis in vivo, ApoE(-/-) mice were injected with an adenovirus expressing human SAA-1, a null virus, or saline. Mice that received adenovirus expressing SAA had increased TGF-beta concentrations in plasma and increased aortic biglycan content compared with mice that received either null virus or saline. Thus, SAA alters vascular proteoglycans in a pro-atherogenic manner via the stimulation of TGF-beta and may play a causal role in the development of atherosclerosis. (Am J Pathol 2008, 173:1902-1910; DOI: 10.2353/ajpath.2008.080201)