Table 1.

Mechanisms of HDL dysfunction during sepsis by alterations in HDL-associated proteins.

Enzyme	Level	Function	Pathology during Sepsis
LCAT	↓	Promotes cholesterol efflux from cells to nascent HDL [84]	Diminished adrenal glucocorticoid function [85] Reduced LPS-neutralizing ability of HDL [86]
CETP	↓	Exchange of CE & TG between HDL and Apo-B-containing lipoproteins; promotes HDL maturation [87]	Missense variant in sepsis patients associated with HDL reduction, decreased survival, and increased organ failure [88]
PLTP	↑	Transfer of amphipathic molecules including phospholipids [89]	Regulates HDL size and composition [90] Recombinant PLTP in mice decreases bacterial growth and accelerates LPS detoxification [91]
PON	↓	Hydrolyzes lipid peroxides	Declines 71% in sepsis day 1–3 [92] Fails to inhibit oxLDL [93,94]
PAF-AH	↓	Hydrolyzes PAF	Declines 90% in sepsis day 1–3 [92] Failure to hydrolyze PAF, leading to immune cell activation, platelet activation, vascular permeability, and hypotension [95] Recombinant PAF-AH had no mortality benefit when used in septic patients [96]
EL	↑	Hydrolyzes HDL particles to liberate FFAs [97]	Upregulation leads to reduced HDL levels [98] Upregulation in inflammatory states may play a role in the resulting low-HDL state [99] EL knockout mice had increased survival to LPS-induced inflammation [100]
SAA	↑	Cytokine-like, propagates APR, modifies HDL transport [101]	>1000-fold increase during APR, displacing Apo-A-I [102] Comprises up to 80% of the proteins in higher-density HDL molecules [103] Increased HDL catabolism [104] Enhanced MDSC survival [105]
PLA2	↑	Hydrolyzes phospholipids to generate an FFA and lysophospholipid	Elevated lipoprotein-associated levels independent predictor of mortality in sepsis [106] Mainly mobilizes AA [107]