The apolipoprotein mimetic peptide 4F prevents sepsis‐induced changes in HDL composition in rodents

Abstract

Clinical studies suggest that sepsis complications are related to both a reduction in plasma HDL and a decrease in HDL functional properties. Our previous studies show that administration of the apoA‐I mimetic peptide 4F to rats undergoing cecal ligation and puncture (CLP) surgery reduces inflammatory injury and improves survival. The goal of the current study was to test the hypothesis that protective effects of 4F are related to an improvement in HDL composition. Male Sprague‐Dawley rats were randomized to undergo CLP or sham surgery. CLP rats were further subdivided to receive saline (n=10) or 4F (10mg/kg, n=10) by ip injection 6 hours after sepsis induction. Sham‐operated rats received saline (n=10). Plasma total cholesterol (TC) and HDL were significantly reduced and lipid hydroperoxide (LOOH) content increased in CLP rats 24 hrs post‐surgery compared to shams. 4F treatment in CLP rats blunted these changes. Compositional analysis of isolated HDL fractions revealed a significant decrease in apoA‐I, apoA‐IV, apoA‐II and apoC and an increase in apoE. The concentration of a protein that was identified by mass spectrometry as serum amyloid A was also increased. 4F normalized these changes in HDL‐associated proteins. It is proposed that the attenuation of sepsis‐induced changes in HDL‐associated proteins by 4F enhances the functional properties of HDL in CLP rats.