Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Radulović, S; Gottschalk, B; Hörl, G; Zardoya-Laguardia, P; Schilcher, I; Hallström, S; Vujić, N; Schmidt, K; Trieb, M; Graier, WF; Malli, R; Kratky, D; Marsche, G; Frank, S.
Endothelial lipase increases eNOS activating capacity of high-density lipoprotein.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020; 1865(4):158612 Doi: 10.1016/j.bbalip.2020.158612 [OPEN ACCESS]
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Leading authors Med Uni Graz

Frank Sasa

Radulovic Snjezana

Co-authors Med Uni Graz

Gottschalk Benjamin

Graier Wolfgang

Hallström Seth

Hörl Gerd

Kratky Dagmar

Malli Roland

Marsche Gunther

Schilcher Irene Rosa Maria

Trieb Markus

Vujic Nemanja

Zardoya Laguardia Pablo

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Abstract:

Endothelial lipase (EL) changes structural and functional properties of high-density lipoprotein (HDL). HDL is a relevant modulator of endothelial nitric oxide synthase (eNOS) activity, but the effect of EL on HDL induced eNOS-activation has not yet been investigated. Here, we examined the impact of EL-modified HDL (EL-HDL) on eNOS activity, subcellular trafficking, and eNOS- dependent vasorelaxation. EL-HDL and empty virus (EV)-HDL as control were isolated from human serum incubated with EL-overexpressing or EV infected HepG2 cells. EL-HDL exhibited higher capacity to induce eNOS phosphorylation at Ser1177 and eNOS activity in EA.hy 926 cells, as well as eNOS-dependent vasorelaxation of mouse aortic rings compared to control HDL. As revealed by confocal and structured illumination-microscopy EL-HDL-driven induction of eNOS was accompanied by an increased eNOS-GFP targeting to the plasma membrane and a lower eNOS-GFP colocalization with Golgi and mitochondria. Widefield microscopy of filipin stained cells revealed that EL-HDL lowered cellular free cholesterol (FC) and as found by thin-layer chromatography increased cellular cholesterol ester (CE) content. Additionally, cholesterol efflux capacity, acyl-coenzyme A: cholesterol acyltransferase activity, and HDL particle uptake were comparable between EL-HDL and control HDL. In conclusion, EL increases eNOS activating capacity of HDL, a phenomenon accompanied by an enrichment of the plasma membrane eNOS pool, a decreased cell membrane FC and increased cellular CE content. Copyright © 2020. Published by Elsevier B.V.

Find related publications in this database (using NLM MeSH Indexing)

Cell Line - administration & dosage

Cell Membrane - metabolism

Cholesterol - metabolism

Enzyme Activation - administration & dosage

Hep G2 Cells - administration & dosage

Humans - administration & dosage

Lipase - metabolism

Lipoproteins, HDL - metabolism

Nitric Oxide Synthase Type III - metabolism

Phosphorylation - administration & dosage

Vasodilation - administration & dosage

Find related publications in this database (Keywords)

eNOS

HDL

Myography

Microscopy

Endothelial lipase

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