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Untargeted Lipidomics Reveals a Specific Enrichment in Plasmalogens in Epicardial Adipose Tissue and a Specific Signature in Coronary Artery Disease.
Arteriosclerosis, Thrombosis, and Vascular Biology ( IF 7.4 ) Pub Date : 2020-02-27 , DOI: 10.1161/atvbaha.120.313955
Magali Barchuk 1 , Anne Dutour 2, 3 , Patricia Ancel 2 , Ljubica Svilar 2, 4 , Veronica Miksztowicz 1, 5 , Graciela Lopez 1 , Miguel Rubio 6 , Laura Schreier 1 , Juan Patricio Nogueira 7 , René Valéro 2, 3 , Sophie Béliard 2, 3 , Jean Charles Martin 2 , Gabriela Berg 1, 5 , Bénédicte Gaborit 2, 3
Affiliation  

OBJECTIVE Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.

中文翻译:

未靶向的脂质组学揭示了心外膜脂肪组织中血浆中特定的致富物和冠状动脉疾病中的特定特征。

目的心外膜脂肪组织(EAT)是一种活跃的内分泌器官,可通过旁分泌释放促动脉粥样硬化的介质来促进冠状动脉疾病(CAD)的病理生理。许多研究已经分析了EAT的炎症特征,但是关于脂质组的信息却很少。我们的目标是首先研究EAT与皮下脂肪组织(SAT)脂质组之间的差异,其次是确定EAT和SAT在CAD中的特定非靶向脂质组学特征。方法和结果:对25例有CAD的患者和14例无CAD的患者进行了皮下和EAT的非靶向脂质体分析,并与分离的VLDL(极低密度脂蛋白)和HDL(高密度脂蛋白)的配对血浆脂质体分析进行了比较。使用正电离和负电离模式,在联用Q-Exactive plus质谱仪的C18色谱柱上进行脂质组学分析。EAT和SAT具有独立的脂质组学特征,与SAT的假发现率= 3×10-4相比,差异表达了95种脂质,磷脂酰乙醇胺18:1p / 22:6在EAT中的表达量增加了20倍。与没有CAD的患者相比,患有CAD的患者的EAT表现出更多的神经酰胺(P = 0.01),甘油二酸酯(P = 0.004;饱和和不饱和),甘油单酸酯(P = 0.013)。相反,它们具有较少的不饱和TG(甘油三酸酯; P = 0.02)。在有和没有CAD的患者之间,在SAT中发现的295种脂质中没有发现差异。发现EAT和血浆脂蛋白之间共有51种脂质。发现TG 18:0/18:0/18:1正相关(r = 0.45,P = 0。019)在EAT和HDL中以及在EAT和VLDL中(r = 0.46,P = 0.02)。结论与SAT不同,CAD与EAT的特定脂质组学特征有关。血浆脂蛋白脂质体仅部分反映了EAT脂质体。
更新日期:2020-03-26
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