Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Lipids Health Dis. 2011 May 9;10:70. doi: 10.1186/1476-511X-10-70.
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.
溶血磷脂酰基 1-磷酸（S1P）与脂蛋白结合存在于血液中，主要与高密度脂蛋白（HDL）结合。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 携带物。
我们在这里评估了人血清中含 HDL 部分的 S1P 及其相关鞘脂的水平与缺血性心脏病（IHD）的发生有何关联。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）204 名受试者血清中含 HDL 部分（不含 LDL 和 VLDL）的 S1P 水平。研究组由血清 HDL 胆固醇（HDL-C）水平较高的个体组成（女性：≥73.5mg/dL；男性：≥61.9mg/dL），并经证实患有 IHD；HDL-C 水平较高且无 IHD 的受试者；血清 HDL-C 水平较低的个体（女性：≤38.7mg/dL；男性：≤34.1mg/dL）和患有 IHD，以及血清 HDL-C 水平较低且无 IHD 的个体。
结果表明，血清中含 HDL 部分的 S1P 水平与 IHD 的发生之间存在高度显著的负相关关系。此外，血清中含 HDL 部分的两种其他鞘脂，二氢-S1P 和 C24:1-神经酰胺，也与 IHD 呈负相关关系。此外，我们还证明了 HDL 上的 S1P 量与 HDL 诱导的内皮细胞屏障信号的幅度相关。
这些发现表明，人血清中含 HDL 部分的鞘脂的组成差异与 IHD 的发生有关，并可能有助于 HDL 在 IHD 中的假定保护作用。
