Impact of Sepsis on High-Density Lipoprotein Metabolism

Alexander C Reisinger; Max Schuller; Harald Sourij; Julia T Stadler; Gerald Hackl; Philipp Eller; Gunther Marsche

doi:10.3389/fcell.2021.795460

Impact of Sepsis on High-Density Lipoprotein Metabolism

Front Cell Dev Biol. 2022 Jan 5:9:795460. doi: 10.3389/fcell.2021.795460. eCollection 2021.

Authors

Alexander C Reisinger¹, Max Schuller², Harald Sourij³, Julia T Stadler⁴, Gerald Hackl¹, Philipp Eller¹, Gunther Marsche⁴

Affiliations

¹ Department of Internal Medicine, Intensive Care Unit, Medical University of Graz, Graz, Austria.
² Department of Internal Medicine, Division of Nephrology, Medical University of Graz, Graz, Austria.
³ Department of Internal Medicine, Division of Endocrinology and Diabetology, Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Graz, Austria.
⁴ Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Graz, Austria.

Abstract

Background: High-density lipoproteins (HDL) are thought to play a protective role in sepsis through several mechanisms, such as promotion of steroid synthesis, clearing bacterial toxins, protection of the endothelial barrier, and antioxidant/inflammatory activities. However, HDL levels decline rapidly during sepsis, but the contributing mechanisms are poorly understood. Methods/Aim: In the present study, we investigated enzymes involved in lipoprotein metabolism in sepsis and non-sepsis patients admitted to the intensive care unit (ICU). Results: In 53 ICU sepsis and 25 ICU non-sepsis patients, we observed significant differences in several enzymes involved in lipoprotein metabolism. Lecithin-cholesterol acyl transferase (LCAT) activity, LCAT concentration, and cholesteryl transfer protein (CETP) activity were significantly lower, whereas phospholipid transfer activity protein (PLTP) and endothelial lipase (EL) were significantly higher in sepsis patients compared to non-sepsis patients. In addition, serum amyloid A (SAA) levels were increased 10-fold in sepsis patients compared with non-sepsis patients. Furthermore, we found that LCAT activity was significantly associated with ICU and 28-day mortality whereas SAA levels, representing a strong inflammatory marker, did not associate with mortality outcomes. Conclusion: We provide novel data on the rapid and robust changes in HDL metabolism during sepsis. Our results clearly highlight the critical role of specific metabolic pathways and enzymes in sepsis pathophysiology that may lead to novel therapeutics.

Keywords: CETP; LCAT (lecithin-cholesterol acyltransferase) activity; PLTP; endothelial lipase (EL); lipoprotein; sepsis.