scholarly journals LDL-apheresis as an alternate method for plasma LPS purification in healthy volunteers, dyslipidemic and septic patients

2020 ◽  
Author(s):  
Auguste Dargent ◽  
Jean-Paul Pais de Barros ◽  
Samir Saheb ◽  
Randa Bittar ◽  
Wilfried Le Goff ◽  
...  
Keyword(s):  
Septic Shock ◽  
Polymyxin B ◽  
Low Density Lipoproteins ◽  
Free Form ◽  
Low Density ◽  
Ldl Apheresis ◽  
Gram Negative Bacteremia ◽  
Phosphate Buffered Saline ◽  
Prime Target

AbstractLipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. Extracorporeal removal method by polymyxin B hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including low density lipoproteins (LDL). Lipoproteins are critical for physiological LPS clearance, as LPS are carried by low density lipoproteins (LDL) to the liver for elimination. We hypothesized that LDL-apheresis can be an alternate method for LPS removal. We demonstrated first in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in phosphate-buffered saline. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL-apheresis for familial hypercholesterolemia is also removed during their LDL-apheresis sessions, both with electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

scholarly journals LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

2020 ◽  
Vol 61 (12) ◽  
pp. 1776-1783
Author(s):  
Auguste Dargent ◽  
Jean-Paul Pais de Barros ◽  
Samir Saheb ◽  
Randa Bittar ◽  
Wilfried Le Goff ◽  
...  
Keyword(s):  
Septic Shock ◽  
Free Form ◽  
Ldl Apheresis ◽  
Direct Hemoperfusion ◽  
Gram Negative ◽  
Improve Outcome ◽  
Gram Negative Bacteremia ◽  
Extracorporeal Removal ◽  
Prime Target

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

Low-density lipoproteins supply phospholipid-bound arachidonic acid for platelet eicosanoid production

1998 ◽  
Vol 275 (5) ◽  
pp. E777-E784 ◽  
Author(s):  
Petra Dobner ◽  
Bernd Engelmann
Keyword(s):  
Arachidonic Acid ◽  
Concentration Dependence ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Ldl Apheresis ◽  
Eicosanoid Production ◽  
Eicosanoid Formation

After the rapid extracorporal reduction of plasma low-density lipoprotein (LDL) by LDL apheresis, the percentages of arachidonic acid (AA)-containing species of phosphatidylcholine (PC) were lowered in the plasma of patients with hypercholesterolemia. The same PC species with AA were also decreased in the patient’s platelets. Thus the supply of phospholipid-bound AA from LDL to the platelets was probably diminished after the apheresis. We therefore analyzed the concentration dependence of the transfer of phospholipid-bound AA from LDL to the platelets under in vitro conditions. The amount of [14C]AA-PC transferred to platelets strongly increased upon elevation of LDL from 0.1 to 1 mg protein/ml, with a less marked elevation being noted at higher LDL concentrations. After stimulation with thrombin (0.5 U/ml), 7.1% ([14C]AA-PC) and 10.6% ([14C]AA-phosphatidylethanolamine) of the14C transferred from LDL to the platelets were recovered in the eicosanoids [14C]thromboxane B2(TxB2) plus 12-[14C]hydroxyeicosatetraenoic acid. Experimental increases and reductions of the [14C]AA-PC import were associated with comparable modifications in the [14C]TxB2production of the platelets. Accordingly, the import of phospholipid-bound [14C]AA is a necessary prerequisite for the formation of14C-labeled eicosanoids. In summary, the transfer of phospholipids from LDL to the platelets markedly varies within the physiological range of lipoprotein concentrations. LDL contributes to platelet eicosanoid formation by supplying platelets with phospholipid-bound AA.

Decreased susceptibility of low-density lipoproteins to in-vitro oxidation after dextran-sulfate LDL-apheresis treatment

1996 ◽  
Vol 126 (2) ◽  
pp. 305-312 ◽  
Author(s):  
Norbert Leitinger ◽  
Christian Pirich ◽  
Ingrid Blazek ◽  
Georg Endler ◽  
Helmut Sinzinger
Keyword(s):  
Dextran Sulfate ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Ldl Apheresis

Nonenzymatic glycosylation of low density lipoproteins in vitro. Effects on cell-interactive properties

Diabetes ◽  
1981 ◽  
Vol 30 (10) ◽  
pp. 875-878 ◽  
Author(s):  
B. Gonen ◽  
J. Baenziger ◽  
G. Schonfeld ◽  
D. Jacobson ◽  
P. Farrar
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Nonenzymatic Glycosylation ◽  
In Vitro Effects

scholarly journals Selective modification of apoB-100 in the oxidation of low density lipoproteins by myeloperoxidase in vitro

1999 ◽  
Vol 40 (4) ◽  
pp. 686-698 ◽  
Author(s):  
Chao-yuh Yang ◽  
Zi-Wei Gu ◽  
Manlan Yang ◽  
Shen-Nan Lin ◽  
Anthony J. Garcia-Prats ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density

scholarly journals Catabolism of human very low density lipoproteins in vitro: a fluorescent phospholipid method for monitoring lipolysis.

1981 ◽  
Vol 22 (2) ◽  
pp. 382-386
Author(s):  
M R Taskinen ◽  
J D Johnson ◽  
M L Kashyap ◽  
K Shirai ◽  
C J Glueck ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins

scholarly journals Sirtuin 3 Restores Synthesis and Secretion of Very Low-Density Lipoproteins in Cow Hepatocytes Challenged with Nonesterified Fatty Acids In Vitro

2021 ◽  
Vol 8 (7) ◽  
pp. 121
Author(s):  
Dongmei Xing ◽  
Baogen Wang ◽  
Hong Lu ◽  
Tao Peng ◽  
Jianming Su ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dairy Cows ◽  
Low Density Lipoproteins ◽  
Mrna Abundance ◽  
Low Density ◽  
Sirtuin 3 ◽  
Very Low Density Lipoproteins ◽  
Nonesterified Fatty Acids ◽  
Tag Accumulation

Fatty liver is closely associated with elevated concentrations of nonesterified fatty acids (NEFA) and a low level of very low-density lipoproteins (VLDL) in blood of dairy cows. High NEFA inhibit the VLDL synthesis and assembly, and cause hepatic triacylglycerol (TAG) deposition. Sirtuin 3 (SIRT3), a mitochondrial deacetylase, antagonizes NEFA-induced TAG accumulation through modulating expressions of fatty acid synthesis and oxidation genes in cow hepatocytes. However, the role of SIRT3 in the VLDL synthesis and assembly was largely unknown. Here we aimed to test whether SIRT3 would recover the synthesis and assembly of VLDL in cow hepatocytes induced by high NEFA. Primary cow hepatocytes were isolated from 3 Holstein cows. Hepatocytes were infected with SIRT3 overexpression adenovirus (Ad-SIRT3), SIRT3-short interfering (si) RNA, or first infected with Ad-SIRT3 and then incubated with 1.0 mM NEFA (Ad-SIRT3 + NEFA). Expressions of key genes in VLDL synthesis and the VLDL contents in cell culture supernatants were measured. SIRT3 overexpression significantly increased the mRNA abundance of microsomal triglyceride transfer protein (MTP), apolipoprotein B100 (ApoB100) and ApoE (p < 0.01), and raised VLDL contents in the supernatants (p < 0.01). However, SIRT3 silencing displayed a reverse effect in comparison to SIRT3 overexpression. Compared with NEFA treatment alone, the Ad-SIRT3 + NEFA significantly upregulated the mRNA abundance of MTP, ApoB100 and ApoE (p < 0.01), and increased VLDL contents in the supernatants (p < 0.01). Our data demonstrated that SIRT3 restored the synthesis and assembly of VLDL in cow hepatocytes challenged with NEFA, providing an in vitro basis for further investigations testing its feasibility against hepatic TAG accumulation in dairy cows during the perinatal period.

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