Reduced expression of adipose triglyceride lipase decreases arachidonic acid release and prostacyclin secretion in human aortic endothelial cells

Arch Physiol Biochem. 2017 Oct;123(4):249-253. doi: 10.1080/13813455.2017.1309052. Epub 2017 Apr 3.

Abstract

Background: Vascular endothelial cells represent an important source of arachidonic acid (AA)-derived mediators involved in the generation of anti- or proatherogenic environments. Evidence emerged (in mast cells), that in addition to phospholipases, neutral lipid hydrolases as adipose triglyceride lipase (ATGL) also participate in this process.

Objective: To examine the impact of ATGL on AA-release from cellular phospholipids (PL) and on prostacyclin secretion in human aortic endothelial cells (HAEC).

Methods and results: siRNA-mediated silencing of ATGL promoted lipid droplet formation and TG accumulation in HAEC (nile red stain). ATGL knockdown decreased the basal and A23187 (calcium ionophore)-induced release of 14C-AA from (14C-AA-labeled) HAEC. In A23187-stimulated ATGL silenced cells, this was accompanied by a decreased content of 14C-AA in cellular PL and a decreased secretion of prostacyclin (determined by 6-keto PGF1α EIA).

Conclusions: In vascular endothelial cells, the efficiency of stimulus-induced AA release and prostacyclin secretion is dependent on ATGL.

Keywords: Arachidonic acid; adipose triglyceride lipase; eicosanoids; phospholipase.

MeSH terms

  • Aorta / cytology
  • Aorta / metabolism*
  • Arachidonic Acid / metabolism*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Epoprostenol / metabolism*
  • Humans
  • Lipase / antagonists & inhibitors
  • Lipase / genetics
  • Lipase / metabolism*
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering
  • Arachidonic Acid
  • Epoprostenol
  • Lipase
  • PNPLA2 protein, human

Grant support

This work was supported by the Austrian Science Fund (FWF; grant P19473-B05 to S.F.) and the Frank Lanyar Foundation of the Medical University Graz, Austria (http://www.medunigraz.at/franz-lanyar-stiftung/) (grant 369 to S.F.). The funding sources had no involvement in study design; collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.