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Gautier T, Deckert V, Nguyen M, et al. New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis. Pharmacol Ther. 2021;108105doi: 10.1016/j.pharmthera.2021.108105.
Gautier, T., Deckert, V., Nguyen, M., Desrumaux, C., Masson, D., & Lagrost, L. (2021). New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis. Pharmacology & therapeutics, 108105. https://doi.org/10.1016/j.pharmthera.2021.108105
Gautier, Thomas, et al. "New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis." Pharmacology & therapeutics vol. (2021): 108105. doi: https://doi.org/10.1016/j.pharmthera.2021.108105
Gautier T, Deckert V, Nguyen M, Desrumaux C, Masson D, Lagrost L. New therapeutic horizons for plasma phospholipid transfer protein (PLTP): Targeting endotoxemia, infection and sepsis. Pharmacol Ther. 2021 Dec 30;108105. doi: 10.1016/j.pharmthera.2021.108105. Epub 2021 Dec 30. PMID: 34974028.
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Pharmacol Ther. 2021 Dec 30;108105. doi: 10.1016/j.pharmthera.2021.108105. Epub 2021 Dec 30.

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

Pharmacology & therapeutics

Thomas Gautier, Valérie Deckert, Maxime Nguyen, Catherine Desrumaux, David Masson, Laurent Lagrost

Affiliations

  1. INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France. Electronic address: [email protected].
  2. INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France.
  3. INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; Service Anesthésie-Réanimation Chirurgicale, Dijon University Hospital, Dijon, France.
  4. INSERM, U1198, Montpellier, France; Faculty of Sciences, Université Montpellier, Montpellier, France.
  5. INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; Plateau Automatisé de Biochimie, Dijon University Hospital, Dijon, France.
  6. INSERM, LNC UMR1231, Dijon, France; University of Bourgogne and Franche-Comté, LNC UMR1231, Dijon, France; FCS Bourgogne-Franche Comté, LipSTIC LabEx, Dijon, France; Service de la Recherche, Dijon University Hospital, Dijon, France. Electronic address: [email protected].

PMID: 34974028 DOI: 10.1016/j.pharmthera.2021.108105

Abstract

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 functionality 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, beyond 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 infection and sepsis. Indeed, emerging evidence supports the role of PLTP, in the context of its association with lipoproteins, 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 patterns, 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, current 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.

Copyright © 2021. Published by Elsevier Inc.

Keywords: Endotoxemia; Infection; Lipopolysaccharides; Lipoprotein; Plasma phospholipid transfer protein; bacteria; sepsis

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