New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis

Phospholipid Transfer Protein (PLTP) transfers amphiphilic lipids between circulating lipoproteins and between lipoproteins, cells and tissues. Indeed, PLTP is a major determinant of the plasma levels, turnover and functional-ity of the main lipoprotein classes: very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). To date, most attention has been focused on the role of PLTP in the context of cardiometabolic diseases, with additional insights in neurodegenerative diseases and immunity. Importantly, be-yond its influence on plasma triglyceride and cholesterol transport, PLTP plays a key role in the modulation of the immune response, with immediate relevance to a wide range of inflammatory diseases including bacterial infec-tion and sepsis. Indeed, emerging evidence supports the role of PLTP, in the context of its association with lipo-proteins, in the neutralization and clearance of bacterial lipopolysaccharides (LPS) or endotoxins. LPS are amphipathic molecules originating from Gram-negative bacteria which harbor major pathogen-associated pat-terns, triggering an innate immune response in the host. Although the early inflammatory reaction constitutes a key step in the anti-microbial defense of the organism, it can lead to a dysregulated inflammatory response and to hemodynamic disorders, organ failure and eventually death. Moreover, and in addition to endotoxemia and acute inflammation, small amounts of LPS in the circulation can induce chronic, low-grade inflammation with long-term consequences in several metabolic disorders such as atherosclerosis, obesity and diabetes. After an updated overview of the role of PLTP in lipid transfer, lipoprotein metabolism and related diseases, cur-rent knowledge of its impact on inflammation, infection and sepsis is critically appraised. Finally, the relevance of PLTP as a new player and novel therapeutic target in the fight against inflammatory diseases is considered. (c) 2021 Published by Elsevier Inc.

Automated summary

Phospholipid Transfer Protein (PLTP) plays a significant role in lipid transfer between lipoproteins and cells in the bloodstream. It affects the transport of triglycerides and cholesterol in the blood and plays a crucial role in immune response and inflammation regulation.