Epicardial Adipose Tissue Ceramides Are Related to Lipoprotein Lipase Activity in Coronary Artery Disease: Unfolding a Missing Link

Abstract

Background: 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. Methods: 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. Results: LPL activity was higher in EAT from CAD ( P <0.001), and in EAT than SAT in both groups ( P <0.001). ANGPTL4 levels were lower, GPIHBP1 and PPARγ levels were higher in EAT from CAD ( P <0.001). In both groups, EAT exhibited more ceramide ( P =0.01), directly associated with LPL activity, being the strongest association with Cer18:1/24:1 ( P <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 ( P =0.03; P <0.001, respectively), the latter directly associated with LPL activity ( r =0.63, P <0.001) GPIHBP1 levels ( r =0.68, P <0.001), and inversely to EAT ANGPTL4 expression ( r =−0.49, P =0.03). Pairwise partial correlation network showed associations among bioactive lipids and LPL and its regulators ( P <0.001 in all cases). Conclusions: 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.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

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“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

Gene expression of ceramide metabolism enzymes in fat depots of different localization in cardiovascular diseases

“…Их активация в различных типах клеток сердечно-сосудис той системы, а именно в кардиомиоцитах, эндотелиальных и гладкомышечных клетках сосудов приводит к высвобождению церамидов и других биоактивных липидов (сфингозин и сфингозин-1-фосфат), обладающих специфической сигнальной способ ностью. ЭЖТ и ПВЖТ, расположенные в непосредственной близо-сти к очагу поражения, являются активными источниками церамидов и представляет собой специфический липидомный признак ИБС, демонстрируя повышенное содержание атерогенных церамидов [16].…”