Impact of High-Density Lipoproteins on Sepsis

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Here, we review the impact of high-density lipoproteins (HDL) on sepsis from the perspective of biochemistry and pathophysiology, epidemiological research, and intervention studies in animals. Pathogen lipid moieties are major ligands for innate immunity receptors, such as toll-like receptors. The binding of pathogen-associated lipids to lipoproteins leads to sequestration, neutralization, and inactivation of their pro-inflammatory effects. Lipoproteins constitute an arm of the innate immune system. Pathogen-associated lipids can be removed from the body via the reverse lipopolysaccharide transport pathway in which HDL play a key role. Independent of the capacity for sequestration, the direct anti-inflammatory effects of HDL may counteract the development of sepsis. Mendelian randomization research using genetic variants associated with HDL cholesterol as an instrumental variable was consistent with a probable causal relationship between increased HDL cholesterol levels and decreased risk of infectious hospitalizations. Low HDL cholesterol independently predicts an adverse prognosis in sepsis both in observational epidemiology and in Mendelian randomization studies. Several HDL-associated enzymes, including phospholipid transfer protein (PLTP) and cholesterol ester transfer protein (CETP), undergo profound changes during sepsis. Potential HDL-directed interventions for treatment of sepsis include apolipoprotein A-I-based therapies, recombinant PLTP, and CETP inhibition.

Consumption of Policosanol (Raydel®) Improves Hepatic, Renal, and Reproductive Functions in Zebrafish: In Vivo Comparison Study among Cuban, Chinese, and American Policosanol

“…Raising the serum HDL-C and lowering the TC and LDL-C is an excellent strategy to maintain healthy longevity by suppressing dyslipidemia and hypertension [ 1 , 2 ]. Dyslipidemia, particularly low HDL-C, is a systemic risk factor for many multi-organ failures, such as acute pancreatitis [ 3 ] and sepsis [ 4 ]. In addition, low HDL-C is also associated with reproduction disorders, such as unexplained female infertility [ 5 ] and erectile dysfunction [ 6 ], as well as cardiovascular risk factors.…”

Clinical biomarker profiles reveals gender differences and mortality factors in sepsis

“…High-density lipoprotein cholesterol (HDL-C) represents the level of high-density lipoproteins (HDL) in the blood, playing a crucial role in immune responses and regulating endothelial function ( 33 , 34 ). Its anti-inflammatory action might slow the progression of sepsis ( 35 ). Current research shows that HDL levels significantly decrease in sepsis patients ( 33 , 36 ), a result matching ours, possibly because sepsis triggers a systemic inflammatory response, leading to the release of inflammatory cytokines like tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) ( 34 ), which inversely correlate with HDL ( 35 ), suggesting that inflammatory factors may indirectly reduce HDL synthesis by inhibiting hepatic lipid metabolism.…”

“…Its anti-inflammatory action might slow the progression of sepsis ( 35 ). Current research shows that HDL levels significantly decrease in sepsis patients ( 33 , 36 ), a result matching ours, possibly because sepsis triggers a systemic inflammatory response, leading to the release of inflammatory cytokines like tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) ( 34 ), which inversely correlate with HDL ( 35 ), suggesting that inflammatory factors may indirectly reduce HDL synthesis by inhibiting hepatic lipid metabolism. In our study, HDL-C was a differential diagnostic indicator of higher efficacy in males than females, showing a more significant decrease in male patients.…”

Patients with Bacterial Sepsis Are Heterogeneous with Regard to Their Systemic Lipidomic Profiles

“…Several previous studies have investigated serum levels of lipoproteins and lipid classes in patients with sepsis; these results have been discussed in several recent reviews [ 98 , 99 , 100 , 101 , 102 ]. First, sepsis patients show decreased levels of High (HDL) and Low density (LDL) lipoproteins, and these levels are inversely correlated with the levels of pro-inflammatory cytokines.…”