Enhancement of anti-inflammatory activities of reconstituted HDL by phosphatidylserine in vivo and in vitro

Presented by: Anatol Kontush (Paris, France)

Because phosphatidylserine appears to be one of the most anti-inflammatory components of human HDL, French researchers evaluated the biological properties of artificial HDL particles enhanced by phosphatidylserine.
Cardiovascular disease involves accumulation of fats, primarily cholesterol, in the arterial wall. As a result, inflammation ensues in the sites of lipid accumulation that resembles inflammatory reaction around wounded skin. Such local reaction facilitates further lipid accumulation and should be quickly resolved. Plasma high-density lipoprotein (HDL) particles possess strong anti-inflammatory properties. HDL contains molecules with different capacities to reduce inflammation.
The research team of Dr Anatol Kontush at the Research Unit 1166 of the National Institute of Health and Medical Research (INSERM) at the Hôpital de la Pitié in Paris, France has recently discovered that one of the most anti-inflammatory molecules present in human HDL includes phosphatidylserine, a phospholipid present in HDL in very low amounts but still highly biologically active. On the basis of this finding, the researchers proposed to include phosphatidylserine in artificial HDL particles which are being developed by several pharmaceutical societies to combat cardiovascular complications following myocardial infarction or stroke. 

Dr Kontush presented the first data on the biological properties of artificial HDL particles enhanced by phosphatidylserine at ISA 2015. Studies have revealed that the novel formulation indeed displays enhanced capacity to reduce inflammatory response in macrophages, key cells that drive inflammation in the arterial wall in response to lipid accumulation. Furthermore, only three intravenous injections of the phosphatidylserine-enhanced particles markedly diminished inflammation in a mouse model of atherosclerosis, which features accelerated lipid accumulation in the arteries. These original data suggest that the novel approach bears a potential to reduce inflammation in the arterial wall in humans, which can be of immediate clinical importance given the fact that inflammatory atherosclerotic plaques are particularly prone to rupture, leading to potentially deadly outcomes.

Source:

ISA2015 Clinical Breakthroughs press release