High-Density Lipoproteins Are Bug Scavengers

Abstract

Lipoproteins were initially defined according to their composition (lipids and proteins) and classified according to their density (from very low- to high-density lipoproteins—HDLs). Whereas their capacity to transport hydrophobic lipids in a hydrophilic environment (plasma) is not questionable, their primitive function of cholesterol transporter could be challenged. All lipoproteins are reported to bind and potentially neutralize bacterial lipopolysaccharides (LPS); this is particularly true for HDL particles. In addition, HDL levels are drastically decreased under infectious conditions such as sepsis, suggesting a potential role in the clearance of bacterial material and, particularly, LPS. Moreover, "omics" technologies have unveiled significant changes in HDL composition in different inflammatory states, ranging from acute inflammation occurring during septic shock to low-grade inflammation associated with moderate endotoxemia such as periodontal disease or obesity. In this review, we will discuss HDL modifications associated with exposure to pathogens including bacteria, viruses and parasites, with a special focus on sepsis and the potential of HDL therapy in this context. Low-grade inflammation associated with atherosclerosis, periodontitis or metabolic syndrome may also highlight the protective role of HDLs in theses pathologies by other mechanisms than the reverse transport of cholesterol.

Lipoprotein concentrations over time in the intensive care unit COVID-19 patients: Results from the ApoCOVID study

“…Notably, we have shown a gradual increase over time in both the HDL-C and LDL-C concentrations. These increases over time could be related to patient improvement, the restoration of normovolemia, a reduced inflammatory state, decreased capillary leakage or increased hepatic HDL synthesis [7,11]. The findings described herein of decreased lipoprotein levels at admission followed by increases over time are in accordance with the studies by Fan et al and Hu et al [30,39].…”

“…To better characterize the relationship between the TC, TG, HDL-C and LDL-C concentrations and the outcomes, we focused on COVID-19 patients with bacterial VAP during their stay in the ICU (n = 29, 64%). The median period of time before the onset of VAP was 7 [3][4][5][6][7][8][9] days, and the median number of VAP episodes for each patient was 2 [1][2][3]. Concentrations of TC, TG, HDL-C, and LDL-C were measured on the day of VAP diagnosis.…”

“…In particular, the dysfunction of lipoproteins (and especially of HDL particles) may be interesting to explore in relation to COVID-19 pneumonia [45,46]. Because no patients in our cohort had bacterial coinfection at admission and owing to the late delay before the onset of VAP (7 [3][4][5][6][7][8][9] days), COVID-19 appears to be an interesting model to 1) study the effects of viral infection and 2) the effect of bacterial VAP on the lipid profile.…”

“…The links between viral infection and lipoproteins are less clear than the association between bacterial infection and lipoproteins [7]. Lipid profiles are reportedly altered during some viral infections, such as dengue, in which Total cholesterol (TC) and lipoprotein levels are frequently low; specifically, a low LDL-C concentration is correlated with severity [28,29].…”

Prolonged bedrest reduces plasma high-density lipoprotein levels linked to markedly suppressed cholesterol efflux capacity

“…Of all lipoproteins, HDL have the highest affinity for binding and neutralizing pathogen-associated lipids (e.g. lipopolysaccharide and lipoteichoic acid) 8,9 , which mediate excessive immune activation in bacterial infections [9][10][11] ; a fact that could also be of particular interest in septic conditions 12 . Specifically, an inverse association of HDL-cholesterol with morbidity, sepsis severity 9 and death from infection or other non-cardiovascular causes 13 is observed, while infusion of reconstituted HDL or HDL mimetic particles decrease morbidity and mortality in experimental sepsis models 14 .…”