Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina (M.B., L.S., G.B.).
Universidad de Buenos Aires, CONICET, Facultad de Farmacia y Bioquímica, Argentina (M.B., V.M., G.B.).
Arterioscler Thromb Vasc Biol. 2022 Aug;42(8):e242-e251. doi: 10.1161/ATVBAHA.122.317840. Epub 2022 Jun 16.
Epicardial adipose tissue (EAT) contributes to coronary artery disease (CAD). EAT presents a specific lipidomic signature, showing increased ceramides and other proinflammatory lipids content. Besides, LPL (lipoprotein lipase) activity in EAT would contribute to its expansion, supplying fatty acids to the tissue. Our aim was to evaluate the relations between LPL activity, regulators of LPL, and ceramides in EAT from CAD patients.
We studied patients undergoing coronary bypass graft (CAD, n=25) and patients without CAD (no CAD, n=14). EAT and subcutaneous AT (SAT) were obtained, tissue LPL activity and its regulator's expression (ANGPTL4, GPIHBP1 [glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1], and PPARγ [peroxisomal proliferator-activated receptor γ]) were assessed. Tissue lipidomes were evaluated by UHPLC-MS, in positive and negative ionization modes.
LPL activity was higher in EAT from CAD (<0.001), and in EAT than SAT in both groups (<0.001). ANGPTL4 levels were lower, GPIHBP1 and PPARγ levels were higher in EAT from CAD (<0.001). In both groups, EAT exhibited more ceramide (=0.01), directly associated with LPL activity, being the strongest association with Cer18:1/24:1 (<0.001). EAT Cer18:1/16:0 to Cer18:1/24:0 and Cer18:1/24:1 to 18:1/24:0 ratios were higher in CAD (=0.03; <0.001, respectively), the latter directly associated with LPL activity (=0.63, <0.001) GPIHBP1 levels (=0.68, <0.001), and inversely to EAT ANGPTL4 expression (=-0.49, =0.03). Pairwise partial correlation network showed associations among bioactive lipids and LPL and its regulators (<0.001 in all cases).
The association between LPL activity, total ceramide, and the atherogenic ceramide ratios highlights the importance of the enzyme and these bioactive lipids contributing to the different metabolic profile of EAT in CAD.
心外膜脂肪组织（EAT）与冠状动脉疾病（CAD）有关。EAT 呈现出特定的脂质组学特征，表现为神经酰胺和其他促炎脂质含量增加。此外，EAT 中的脂蛋白脂酶（LPL）活性会促进其扩张，为组织提供脂肪酸。我们的目的是评估 CAD 患者的 EAT 中 LPL 活性、LPL 调节剂与神经酰胺之间的关系。
我们研究了接受冠状动脉旁路移植术的患者（CAD，n=25）和无 CAD 的患者（无 CAD，n=14）。获取 EAT 和皮下脂肪组织（SAT），评估组织 LPL 活性及其调节剂的表达（ANGPTL4、GPIHBP1[糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1]和 PPARγ[过氧化物酶体增殖物激活受体 γ]）。通过 UHPLC-MS 在正、负离子模式下评估组织脂质组学。
CAD 患者的 EAT 中 LPL 活性更高（<0.001），且在两组患者中 EAT 中的 LPL 活性均高于 SAT（均<0.001）。CAD 患者的 EAT 中 ANGPTL4 水平较低，GPIHBP1 和 PPARγ 水平较高（均<0.001）。在两组患者中，EAT 中神经酰胺含量更高（=0.01），与 LPL 活性直接相关，Cer18:1/24:1 与神经酰胺的相关性最强（<0.001）。CAD 患者的 EAT Cer18:1/16:0 至 Cer18:1/24:0 和 Cer18:1/24:1 至 18:1/24:0 比值较高（分别为=0.03；<0.001），后者与 LPL 活性直接相关（=0.63，<0.001），与 GPIHBP1 水平相关（=0.68，<0.001），与 EAT ANGPTL4 表达呈负相关（=-0.49，=0.03）。两两部分相关网络显示生物活性脂质与 LPL 及其调节剂之间存在关联（在所有情况下均<0.001）。
LPL 活性、总神经酰胺和致动脉粥样硬化神经酰胺比值之间的关联突出了该酶和这些生物活性脂质对 CAD 患者 EAT 不同代谢特征的重要性。
