S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease.

S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease.
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DOI:
10.1186/1476-511x-10-70
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发表时间:
2011-05-09
影响因子:
4.5
通讯作者:
Argraves WS
Argraves WS
中科院分区:
医学3区
文献类型:
--
作者:
Argraves KM;Sethi AA;Gazzolo PJ;Wilkerson BA;Remaley AT;Tybjaerg-Hansen A;Nordestgaard BG;Yeatts SD;Nicholas KS;Barth JL;Argraves WS

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溶鞘磷脂1-磷酸鞘磷脂(S1P)在血液中携带与脂蛋白,主要是高密度脂蛋白(HDL)有关。新出现的证据表明,HDL对心血管功能的许多影响可能归因于其S1P货物。在这里,我们评估了人类血清中含有高密度脂蛋白的部分中S1P和相关鞘脂的水平如何与缺血性心脏病(IHD)的发生相关。为了实现这一目标,我们使用液相色谱-质谱法测量了哥本哈根城市心脏研究(CCHS)中204名受试者血清中含高密度脂蛋白部分(低密度脂蛋白和低密度脂蛋白的缺失)中的S1P水平。研究组包括血清高密度脂蛋白胆固醇(HDL- c)高的个体(女性:≥73.5 mg/dL;男性:≥61.9 mg/dL)和确诊的IHD;高HDL-C且无IHD的受试者;低HDL-C(女性:≤38.7 mg/dL;男性:≤34.1 mg/dL)和IHD患者,低HDL-C但无IHD患者。结果显示血清含高密度脂蛋白部分中S1P水平与IHD的发生呈极显著的负相关。此外,在含hdl的血清中,还观察到另外两种鞘脂,二氢- s1p和c24:1 -神经酰胺,与IHD呈负相关。此外,我们证明了高密度脂蛋白中S1P的含量与高密度脂蛋白诱导的内皮细胞屏障信号传导的大小相关。这些发现表明,人血清中含HDL部分鞘脂的组成差异与IHD的发生有关,并可能有助于推测HDL在IHD中的保护作用。
The lysosphingolipid sphingosine 1-phosphate (S1P) is carried in the blood in association with lipoproteins, predominantly high density lipoproteins (HDL). Emerging evidence suggests that many of the effects of HDL on cardiovascular function may be attributable to its S1P cargo. Here we have evaluated how levels of S1P and related sphingolipids in an HDL-containing fraction of human serum correlate with occurrence of ischemic heart disease (IHD). To accomplish this we used liquid chromatography-mass spectrometry to measure S1P levels in the HDL-containing fraction of serum (depleted of LDL and VLDL) from 204 subjects in the Copenhagen City Heart Study (CCHS). The study group consisted of individuals having high serum HDL cholesterol (HDL-C) (females:≥73.5 mg/dL; males:≥61.9 mg/dL) and verified IHD; subjects with high HDL-C and no IHD; individuals with low HDL-C (females:≤38.7 mg/dL; males:≤34.1 mg/dL) and IHD, and subjects with low HDL-C and no IHD. The results show a highly significant inverse relationship between the level of S1P in the HDL-containing fraction of serum and the occurrence of IHD. Furthermore, an inverse relationship with IHD was also observed for two other sphingolipids, dihydro-S1P and C24:1-ceramide, in the HDL-containing fraction of serum. Additionally, we demonstrated that the amount of S1P on HDL correlates with the magnitude of HDL-induced endothelial cell barrier signaling. These findings indicate that compositional differences of sphingolipids in the HDL-containing fraction of human serum are related to the occurrence of IHD, and may contribute to the putative protective role of HDL in IHD.