Phosphatidylserine improves the anti-inflammatory function of high density lipoproteins (HDL)

Chronic inflammatory diseases impact the lives of many people and represent a significant cost to our healthcare system today.

They can be treated using anti-inflammatory drugs of natural or synthetic origin. In the human body, a wide variety of molecules have anti-inflammatory properties that can help fight against these diseases.

Recent research conducted at IHU ICAN by Dr. Maryam Darabi and Dr. Anatol Kontush has demonstrated that the inclusion of phosphatidylserine significantly enhances the anti-inflammatory function of reconstituted high-density lipoprotein (rHDL).

How can this approach be used to treat certain chronic inflammatory diseases?

What are the objectives of this research?

Phosphatidylserine (PS) is a substance produced by the body that makes up the bulk of the cell membrane. Phosphatidylserine is a phospholipid that helps resolve inflammation. Indeed, it is one of the main “eat-me” signals involved in the elimination of apoptotic cells by immune cells.

Reconstituted HDL particles. In green, apolipoprotein A-I, the main protein of HDL. In yellow, phosphatidylcholine, the main lipid of HDL.

Present in the blood, human high-density lipoprotein (HDL) is a multimolecular complex with a strong capacity to reduce inflammation. It contains a set of lipid and protein molecules, a minority of which is phosphatidylserine (PS).

Using their major lipid and protein components, HDL (human high density lipoprotein) particles can be artificially reconstituted using apolipoprotein A-I (the major protein of HDL) and phosphatidylcholine (the major lipid of HDL) and thus used as therapeutic agents.

What are the results?

Macrophages are key cells in the body involved in the development of chronic inflammatory diseases.

The results were obtained in vitro using the THP-1 human macrophage cell line, but also with primary human macrophages prepared from circulating monocytes.

  • Research has shown that the inclusion of phosphatidylserine (PS) in reconstituted HDL improves its ability to reduce inflammation, with superior anti-inflammatory function to “standard” HDL without PS.
  • In particular, HDL with PS helps to further reduce the secretion and expression of interleukin-6 (an inflammatory molecule) by macrophages.
  • Finally, they also show superior anti-inflammatory properties in vivo in a mouse model of dyslipidemia and chronic inflammation.

HDL formulations were administered to dyslipidemic mice on a high-cholesterol diet to induce atherosclerosis and chronic inflammation.

In conclusion, phosphatidylserine has been shown to be a potent anti-inflammatory component capable of enhancing the therapeutic potential of HDL-based therapy. These results represent a promising new approach to the treatment of chronic inflammatory diseases.

Who are the actors involved?

The research work was mainly carried out within the UMRS 1166 (AP-HP, Inserm, Sorbonne University, IHU ICAN):

  • By Dr. Maryam Darabi (Postdoctoral Researcher),
  • Under the supervision of Dr. Anatol Kontush (Research Director),
  • In collaboration with the ICAN Omics Lipidomics platform,
  • And supported by SATT-Lutech, INSERM and Sorbonne University.

The results of this research were reported in the scientific article “Phosphatidylserine Enhances Anti-inflammatory Effects of Reconstituted HDL in Macrophages via Distinct Intracellular Pathways”, published in The Faseb Journal on April 13, 2022.