Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia.
Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia.
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DOI：
10.1038/s41598-020-73411-7
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发表时间：
2020-09-30
影响因子：
4.6
通讯作者：
Barile L
中科院分区：
文献类型：
--
作者：
Burrello J;Biemmi V;Dei Cas M;Amongero M;Bolis S;Lazzarini E;Bollini S;Vassalli G;Paroni R;Barile L
鞘磷脂是细胞膜的结构成分，在细胞信号转导中发挥多种功能。细胞外小泡(EV)是一种脂质双层膜纳米颗粒，其脂质组成可能与亲本细胞不同，尤其是在病理条件下，鞘磷脂类物质中的EV含量显著增加。我们的目的是优化EV从血浆中的分离，并描述EV与全血浆相比的不同脂肪含量。作为初步研究，我们评估了在诊断为ST段抬高型心肌梗死(STEMI)的患者中循环EV的脂组征象的诊断潜力。对STEMI患者于再通前和直接经皮冠状动脉介入治疗后24小时进行评价。用液相色谱质谱联用法对20种鞘磷脂进行了定量。EV-神经酰胺、-二氢神经酰胺和-鞘磷脂在STEMI组较对照组升高，再灌流后降低。它们的水平与肌钙蛋白、白细胞计数和射血分数相关。血浆鞘磷脂水平是EV含量的500到700倍；然而，STEMI患者和对照组之间只有鞘磷脂水平不同。不同种类的鞘脂富含EV及其线性组合，通过机器学习算法在介入治疗前评估中准确地对STEMI患者进行分类。综上所述，EV脂质征象是STEMI患者的鉴别诊断指标。这些发现可能有助于识别与心肌缺血相关的新的生物标志物和信号机制。
Sphingolipids are structural components of cell membrane, displaying several functions in cell signalling. Extracellular vesicles (EV) are lipid bilayer membrane nanoparticle and their lipid composition may be different from parental cells, with a significant enrichment in sphingolipid species, especially in pathological conditions. We aimed at optimizing EV isolation from plasma and describing the differential lipid content of EV, as compared to whole plasma. As pilot study, we evaluated the diagnostic potential of lipidomic signature of circulating EV in patients with a diagnosis of ST-segment-elevation myocardial infarction (STEMI). STEMI patients were evaluated before reperfusion and 24-h after primary percutaneous coronary intervention. Twenty sphingolipid species were quantified by liquid-chromatography tandem-mass-spectrometry. EV-ceramides, -dihydroceramides, and -sphingomyelins increased in STEMI vs. matched controls and decreased after reperfusion. Their levels correlated to hs-troponin, leucocyte count, and ejection fraction. Plasma sphingolipids levels were 500-to-700-fold higher as compared to EV content; nevertheless, only sphingomyelins differed in STEMI vs. control patients. Different sphingolipid species were enriched in EV and their linear combination by machine learning algorithms accurately classified STEMI patients at pre-PCI evaluation. In conclusion, EV lipid signature discriminates STEMI patients. These findings may contribute to the identification of novel biomarkers and signaling mechanisms related to cardiac ischemia.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
他莫昔芬通过调节细胞内神经酰胺来增强中性粒细胞的先天免疫功能。
影响因子：
16.6
作者：
Corriden R;Hollands A;Olson J;Derieux J;Lopez J;Chang JT;Gonzalez DJ;Nizet V
通讯作者：
Nizet V
影响因子：
3.3
作者：
Ibanez, Borja;James, Stefan;Widimsky, Petr
通讯作者：
Widimsky, Petr
影响因子：
8
作者：
Kavaliauskiene, Simona;Nymark, Carl-Martin;Sandvig, Kirsten
通讯作者：
Sandvig, Kirsten
影响因子：
12.4
作者：
Biemmi, Vanessa;Milano, Giuseppina;Barile, Lucio
通讯作者：
Barile, Lucio