Newly developed reconstituted high-density lipoprotein containing sphingosine-1-phosphate induces endothelial tube formation
Newly developed reconstituted high-density lipoprotein containing sphingosine-1-phosphate induces endothelial tube formation
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DOI：
10.1016/j.atherosclerosis.2006.10.020
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发表时间：
2007-09-01
期刊：
影响因子：
5.3
通讯作者：
Saku, Keijiro
中科院分区：
文献类型：
--
作者：
Matsuo, Yoshino;Miura, Shin-Ichiro;Saku, Keijiro
重组高密度脂蛋白(RHDL)已被证明能在动物模型和人类中产生快速的动脉粥样硬化消退。鞘氨醇-L-磷酸(S L P)是高密度脂蛋白中的一种生物活性脂质，在有丝分裂、内皮细胞运动、细胞存活以及组织和分化成血管等方面发挥作用。在本研究中，我们研究了一种新的重组高密度脂蛋白[POPC(1-Palmitoyl-2-油酰磷脂酰胆碱)/S L P/载脂蛋白A-I(A-L)]重组高密度脂蛋白在内皮细胞管状形成和巨噬细胞胆固醇外流中的直接作用。(POPC/S L P/A-I)重组人高密度脂蛋白对巨噬细胞胆固醇流出的影响与常规重组人高密度脂蛋白相似。此外，(POPC/S I P/A-I)重组高密度脂蛋白通过激活磷酸化Akt和磷酸化细胞外信号调节蛋白激酶(p-ERK)1/2和EC管形成来诱导EC增殖，这种作用可被Akt、ERK和内皮型一氧化氮合酶(ENOS)抑制剂所阻断。此外，(P0PC/S1P/A-I)rHDL诱导的p-ERK1/2激活和EC管的形成主要归因于反义策略确定的SLP通过SIP2和SIP3突变的信号。综上所述，(POPC/S[P/A-I])重组高密度脂蛋白诱导的胆固醇外流不依赖于SIP2，但在AKT/ERK/NO通过SIP2和SIP3介导的EC小管形成中具有额外的SIP3介导的作用。在未来，这些新的圆盘可能会用于治疗动脉粥样硬化和缺血性心血管疾病，如急性冠状动脉综合征和动脉粥样硬化闭塞症。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
Reconstituted high-density lipoprotein (rHDL) has been shown to produce a rapid regression of atherosclerosis in animal models and humans. Sphingosine-l-phosphate (S l P), which is a bioactive lipid in HDL, plays a role in mitogenesis, endothelial cell motility, and cell survival, as well as organization and differentiation into a vessel. In this study, we examined the direct role of a newly developed rHDL, [POPC(1-palmitoyl-2-oleoyl phosphatidylcholine)/S l P/apolipoproteinA-I(A-l)]rHDL containing S I P in tube formation in endothelial cells (ECs) as well as cholesterol efflux in macrophage. The effect of (POPC/S l P/A-I)rHDL on cholesterol efflux in macrophage was similar to that of conventional rHDL, (POPC/A-I)rHDL. In addition, (POPC/S I P/A-I)rHDL induced EC proliferation through the activation of phospho-Akt and phospho-extracellular-signal-regulated kinases (p-ERK) 1/2 and EC tube formation, and this effect was blocked by inhibitors of Akt, ERK and endothelial nitric-oxide synthase (eNOS). In addition, (P0PC/S1P/A-I)rHDL-induced p-ERK1/2 activation and EC tube formation can be mainly attributed to SlP-stimutated signaling through SIP2 and SIP3 as determined by an anti-sense strategy. In conclusion, (POPC/S]P/A-I)rHDL induces cholesterol efflux independently of SIP but has additional SIP-mediated effects on EC tube formation mediated by Akt/ERK/NO through SIP2 and SIP3. In the future, these new discs may be useful for the treatment of atherosclerotic and ischernic cardiovascular disease, such as acute coronary syndrome and atherosclerosis obliterans. (C) 2006 Elsevier Ireland Ltd. All rights reserved.