Impact of Sepsis on High-Density Lipoprotein Metabolism

Reisinger, Alexander Christian; Schüller, Max; Sourij, Harald; Stadler, Julia T.; Hackl, Gerald; Eller, Philipp; Marsche, Gunther

doi:10.3389/fcell.2021.795460

Cited by 17 publications

(22 citation statements)

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“…The major functions of human SAA are associated with amyloidogenesis, the remodeling of HDL, tumor pathogenesis, anti-bacterial functions, and regulation of inflammation and immunity [ 105 ]. In sepsis, patients in the critical phase showed that the HDL-C level decreased to approximately 14 mg/dL, while SAA sharply elevated to around 2827 μg/mL, in contrast to the control group that showed a normal level of HDL-C (~39 mg/dL) and 269 μg/mL of SAA [ 106 ]. SAA is expressed almost exclusively in the liver and is triggered by pro-inflammatory cytokines.…”

Section: Hdl Qualitymentioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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The quantity of high-density lipoproteins (HDL) is represented as the serum HDL-C concentration (mg/dL), while the HDL quality manifests as the diverse features of protein and lipid content, extent of oxidation, and extent of glycation. The HDL functionality represents several performance metrics of HDL, such as antioxidant, anti-inflammatory, and cholesterol efflux activities. The quantity and quality of HDL can change during one’s lifetime, depending on infection, disease, and lifestyle, such as dietary habits, exercise, and smoking. The quantity of HDL can change according to age and gender, such as puberty, middle-aged symptoms, climacteric, and the menopause. HDL-C can decrease during disease states, such as acute infection, chronic inflammation, and autoimmune disease, while it can be increased by regular aerobic exercise and healthy food consumption. Generally, high HDL-C at the normal level is associated with good HDL quality and functionality. Nevertheless, high HDL quantity is not always accompanied by good HDL quality or functionality. The HDL quality concerns the morphology of the HDL, such as particle size, shape, and number. The HDL quality also depends on the composition of the HDL, such as apolipoproteins (apoA-I, apoA-II, apoC-III, serum amyloid A, and α-synuclein), cholesterol, and triglyceride. The HDL quality is also associated with the extent of HDL modification, such as glycation and oxidation, resulting in the multimerization of apoA-I, and the aggregation leads to amyloidogenesis. The HDL quality frequently determines the HDL functionality, which depends on the attached antioxidant enzyme activity, such as the paraoxonase and cholesterol efflux activity. Conventional HDL functionality is regression, the removal of cholesterol from atherosclerotic lesions, and the removal of oxidized species in low-density lipoproteins (LDL). Recently, HDL functionality was reported to expand the removal of β-amyloid plaque and inhibit α-synuclein aggregation in the brain to attenuate Alzheimer’s disease and Parkinson’s disease, respectively. More recently, HDL functionality has been associated with the susceptibility and recovery ability of coronavirus disease 2019 (COVID-19) by inhibiting the activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The appearance of dysfunctional HDL is frequently associated with many acute infectious diseases and chronic aging-related diseases. An HDL can be a suitable biomarker to diagnose many diseases and their progression by monitoring the changes in its quantity and quality in terms of the antioxidant and anti-inflammatory abilities. An HDL can be a protein drug used for the removal of plaque and as a delivery vehicle for non-soluble drugs and genes. A dysfunctional HDL has poor HDL quality, such as a lower apoA-I content, lower antioxidant ability, smaller size, and ambiguous shape. The current review analyzes the recent advances in HDL quantity, quality, and functionality, depending on the health and disease state during one’s lifetime.

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Section: Hdl Qualitymentioning

confidence: 99%

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Cho

2022

IJMS

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“…Reconstituted HDL (rHDL) was prepared using the sodium cholate dialysis method [47] at an initial molar ratio of 95:5:1:0, 95:5:1:0.5, 95:5:1:1, and 95:5:1:2 for POPC:cholesterol:apoA-I:SAA, respectively. The physiological concentration of SAA, around 0.269 mg/mL [10], was mimicked using 0.23 mg and 0.46 mg of SAA for the 1:0.5 and 1:1 molar ratio, respectively, of apoA-I:SAA in 1 mL. The size and hydrodynamic diameter of the rHDL particles were determined by 8-25% native polyacrylamide gradient gel electrophoresis (PAGGE, Pharmacia Phast system) and by a comparison with standard globular proteins (GE healthcare, Cat# 17-0445-01).…”

Section: Synthesis Of Reconstituted Hdlmentioning

confidence: 99%

“…Circulating SAA plays a critical role in various inflammatory diseases, including sepsis, atherosclerosis, and rheumatoid arthritis [9]. In sepsis, patients in the critical phase showed that the HDL-C level was decreased to approximately 14 mg/dL, while SAA was elevated sharply around 2827 µg/mL, while the control group showed a normal level of HDL-C (~39 mg/dL) and 269 µg/mL of SAA [10]. SAA is expressed almost exclusively in the liver and released into the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

“…Many studies have focused on the physiological effects of SAA in the HDL state. On the other hand, although a few studies compared the effect of SAA on HDL quality [7,10,11,14], there is little information on the change in the structural-functional correlation of apoA-I in reconstituted HDL (rHDL) in the absence or presence of SAA. Therefore, it is necessary to investigate the interaction between apoA-I and SAA in lipid free-state and the change in apoA-I structure in SAA-enriched HDL.…”

Section: Introductionmentioning

confidence: 99%

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Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

Cho

2022

Molecules

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Human serum amyloid A (SAA) is an exchangeable apolipoprotein (apo) in high-density lipoprotein (HDL) that influences HDL quality and functionality, particularly in the acute phase of inflammation. On the other hand, the structural and functional correlations of HDL containing SAA and apoA-I have not been reported. The current study was designed to compare the change in HDL quality with increasing SAA content in the lipid-free and lipid-bound states in reconstituted HDL (rHDL). The expressed recombinant human SAA1 (13 kDa) was purified to at least 98% and characterized in the lipid-free and lipid-bound states with apoA-I. The dimyristoyl phosphatidylcholine (DMPC) binding ability of apoA-I was impaired severely by the addition of SAA, while SAA alone could not bind with DMPC. The recombinant human SAA1 was incorporated into the rHDL (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): cholesterol: apoA-I) with various apoA-I:SAA molar ratios from 1:0 to 1:0.5, 1:1 and 1:2. With increasing SAA1 content, the rHDL particle size was reduced from 98 Å to 93 Å, and the α-helicity of apoA-I:SAA was decreased from 73% to 40% for (1:0) and (1:2), respectively. The wavelength maximum fluorescence (WMF) of tryptophan in rHDL was red-shifted from 339 nm to 345 nm for (1:0) and (1:2) of apoA-I:SAA, respectively, indicating that the addition of SAA to rHDL destabilized the secondary structure of apoA-I. Upon denaturation by urea treatment from 0 M to 8 M, SAA showed only a 3 nm red-shift in WMF, while apoA-I showed a 16 nm red-shift in WMF, indicating that SAA is resistant to denaturation and apoA-I had higher conformational flexibility than SAA. The glycation reaction of apoA-I in the presence of fructose was accelerated up to 1.8-fold by adding SAA in a dose-dependent manner than that of apoA-I alone. In conclusion, the incorporation of SAA in rHDL impaired the structural stability of apoA-I and exacerbated glycation of HDL and apoA-I.

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“…HDL-C levels had the strongest correlation with IL-6 and procalcitonin levels, as well as sequential organ failure assessment [ 30 ]. HDLs are thought to play a protective role in sepsis as alterations in HDL metabolism, such as a decrease in lecithin-cholesterol acyl transferase activity and concentration, cholesteryl transfer protein activity, or an increase in phospholipid transfer activity protein and endothelial lipase activity, occur early after the development of sepsis [ 31 ]. Because of its early decrease and high stability, HDL-C is considered to be an independent predictive marker of adverse outcomes and survival in severe sepsis [ 32 ].…”

Section: Membrane and Serum Cholesterol And Their Roles During Infectionmentioning

confidence: 99%

The Influence of SARS-CoV-2 Infection on Lipid Metabolism—The Potential Use of Lipid-Lowering Agents in COVID-19 Management

et al. 2022

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Several studies have indicated lipid metabolism alterations during COVID-19 infection, specifically a decrease in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) concentrations and an increase in triglyceride (TG) levels during the infection. However, a decline in triglycerides can also be observed in critical cases. A direct correlation can be observed between a decrease in serum cholesterol, HDL-C, LDL-C and TGs, and the severity of the disease; these laboratory findings can serve as potential markers for patient outcomes. The transmission of coronavirus increases proportionally with rising levels of cholesterol in the cell membrane. This is due to the fact that cholesterol increases the number of viral entry spots and the concentration of angiotensin-converting enzyme 2 (ACE2) receptor, crucial for viral penetration. Studies have found that lower HDL-C levels correspond with a higher susceptibility to SARS-CoV-2 infection and infections in general, while higher HDL-C levels were related to a lower risk of developing them. However, extremely high HDL-C levels in serum increase the risk of infectious diseases and is associated with a higher risk of cardiovascular events. Low HDL-C levels are already accepted as a marker for risk stratification in critical illnesses, and higher HDL-C levels prior to the infection is associated with a lower risk of death in older patients. The correlation between LDL-C levels and disease severity is still unclear. However, TG levels were significantly higher in non-surviving severe patients compared to those that survived; therefore, elevated TG-C levels in COVID-19 patients may be considered an indicator of uncontrolled inflammation and an increased risk of death.

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Impact of Sepsis on High-Density Lipoprotein Metabolism

Cited by 17 publications

References 50 publications

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

The Current Status of Research on High-Density Lipoproteins (HDL): A Paradigm Shift from HDL Quantity to HDL Quality and HDL Functionality

Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

The Influence of SARS-CoV-2 Infection on Lipid Metabolism—The Potential Use of Lipid-Lowering Agents in COVID-19 Management

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