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.
Highlights
Sepsis accounts for a major proportion of intensive care patients and is a key factor for mortality and morbidity worldwide (Rhee et al, 2019; Rudd et al, 2020)
We were recently able to show that the arylesterase activity (AEA) consistently predicted the intensive care unit (ICU)- and 28day mortality of patients with sepsis and septic shock admitted to the ICU (Reisinger et al, 2020)
We investigated which enzymes involved in lipoprotein metabolism are altered in sepsis and non-sepsis patients in the intensive care unit (ICU)
Summary
Sepsis accounts for a major proportion of intensive care patients and is a key factor for mortality and morbidity worldwide (Rhee et al, 2019; Rudd et al, 2020). Lipid Metabolism in Sepsis diagnosis and prognosis prediction of septic patients. Lipid profiles are commonly affected during sepsis (van Leeuwen et al, 2003; Lekkou et al, 2014; Cirstea et al, 2017). Both compositional changes, such as a rapid decrease of highdensity lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC) levels occur, as well as functional changes such as reduced arylesterase activity (AEA) of the high-density lipoprotein (HDL) associated paraoxonase 1 (PON1) or cholesterol efflux capacity (CEC). We were recently able to show that the AEA consistently predicted the ICU- and 28day mortality of patients with sepsis and septic shock admitted to the ICU (Reisinger et al, 2020). HDL levels decline rapidly during sepsis, but the contributing mechanisms are poorly understood
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