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Biosynthesis of Proresolving Lipid Mediators by Vascular Cells and Tissues

Cells of the immune system have been shown to produce specialized pro-resolving mediators (SPMs), a group of lipid molecules that coordinate the active resolution of inflammation. However, the capacity for non-immune cells types to biosynthesize SPMs is not well understood.

In this publication, Chatterjee et al., aimed to examine this ability by using freshly harvested segments of aortic branch as well as vascular smooth muscle cells and vascular endothelial cells all isolated from human volunteers perioperatively.

The vascular cells and tissues obtained by the researchers were treated with equal concentrations of the fatty acid docosahexaenoic acid (DHA) or 17-HDHA, an SPM which can give rise to down-stream D-series resolvins which have demonstrated beneficial effect in models of atherosclerosis.

They found:

  • In the human aortic branch, DHA and 17-HDHA increased synthesis of D-series resolvins, with 17-HDHA increasing specific resolvins to a greater extent than DHA (e.g. RvD1 and RvD4).
  • In vascular smooth muscle cells and vascular endothelial cells, 17-HDHA led to an approximately 6-fold increase in the biosynthesis of D-series resolvins.
  • When the cell culture media containing the secreted SPMs from the above experiments was used in further experiments with fresh vascular endothelial cells, a reduction in monocyte adhesion was seen, showing a functional effect of SPMs produced by vascular cells.

Why is this Clinically Relevant?

  • Inflammation plays a central role in the development and progression of vascular dysfunction including atherosclerosis and vascular restenosis
  • Mounting evidence shows that SPMs may have a vascular-protective effect
    • Recent studies have described a reduction in the ratio of SPMs/pro-inflammatory lipid mediators in human vulnerable atherosclerotic plaques
    • Pre-clinical studies suggest benefit in models of atherosclerosis and vascular injury, and mechanistic studies in vascular cells have shown that SPM treatment reduced migration, monocyte adhesion, and pro-inflammatory markers
  • That vascular tissue and cells can utilize fatty acids of 17-HDHA present within the tissue or from the circulation for the biosynthesis of SPMs with known vascular benefits, suggests that locally derived SPMs can play a role in vascular homeostasis

Link to the abstract

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