scholarly journals Increased Phospholipid Transfer Protein Activity Is Associated With Markers of Enhanced Lipopolysaccharide Clearance in Human During Cardiopulmonary Bypass

2021 ◽  
Vol 8 ◽  
Author(s):  
Maxime Nguyen ◽  
Thomas Gautier ◽  
Guillaume Reocreux ◽  
Gaëtan Pallot ◽  
Guillaume Maquart ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Adverse Events ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Operative Complications ◽  
Phospholipid Transfer ◽  
Pltp Activity

Introduction: Lipopolysaccharide (LPS) is a component of gram-negative bacteria, known for its ability to trigger inflammation. The main pathway of LPS clearance is the reverse lipopolysaccharide transport (RLT), with phospholipid transfer protein (PLTP) and lipoproteins playing central roles in this process in experimental animal models. To date, the relevance of this pathway has never been studied in humans. Cardiac surgery with cardiopulmonary bypass is known to favor LPS digestive translocation. Our objective was to determine whether pre-operative PLTP activity and triglyceride or cholesterol-rich lipoprotein concentrations were associated to LPS concentrations in patients undergoing cardiac surgery with cardiopulmonary bypass.Methods: A post-hoc analysis was conducted on plasma samples obtained from patients recruited in a randomized controlled trial.Total cholesterol, high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc), triglyceride and PLTP activity were measured before surgery. LPS concentration was measured by mass spectrometry before surgery, at the end of cardiopulmonary bypass and 24 h after admission to the intensive care unit.Results: High PLTP activity was associated with lower LPS concentration but not with inflammation nor post-operative complications. HDLc, LDLc and total cholesterol were not associated with LPS concentration but were lower in patients developing post-operative adverse events. HDLc was negatively associated with inflammation biomarkers (CRP, PCT). Triglyceride concentrations were positively correlated with LPS concentration, PCT and were higher in patients with post-operative complications.Conclusion: Our study supports the role of PLTP in LPS elimination and the relevance of RLT in human. PLTP activity, and not cholesterol rich lipoproteins pool size seemed to be the limiting factor for RLT. PLTP activity was not directly related to post-operative inflammation and adverse events, suggesting that LPS clearance is not the main driver of inflammation in our patients. However, HDLc was associated with lower inflammation and was associated with favorable outcomes, suggesting that HDL beneficial anti-inflammatory effects could be, at least in part independent of LPS clearance.

scholarly journals Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution

2002 ◽  
Vol 43 (8) ◽  
pp. 1256-1263 ◽  
Author(s):  
Susan J. Murdoch ◽  
Molly C. Carr ◽  
Hal Kennedy ◽  
John D. Brunzell ◽  
John J. Albers
Keyword(s):  
Hepatic Lipase ◽  
Premenopausal Women ◽  
Plasma Lipoproteins ◽  
Cholesterol Concentration ◽  
Phospholipid Transfer Protein ◽  
Transfer Protein ◽  
Phospholipid Transfer ◽  
Pltp Activity ◽  
Hdl Metabolism ◽  
Relationship Of

Phospholipid transfer protein (PLTP), hepatic lipase (HL), and lipoprotein lipase (LPL) have all been reported to be intricately involved in HDL metabolism but the effect of PLTP on the apolipoprotein B-containing lipoproteins relative to that of HL and LPL has not been established. Due to our previous observation of a positive correlation of PLTP activity with plasma apoB and LDL cholesterol, the relationship of PLTP with the LDL subfractions was investigated and compared with that of HL and LPL. Plasma lipoproteins from 50 premenopausal women were fractionated by density gradient ultracentrifugation. Correlations were calculated between the cholesterol concentration of each fraction and plasma PLTP, HL, and LPL activity. Plasma PLTP activity was highly, positively, and selectively correlated with the cholesterol concentration of the buoyant LDL/dense IDL fractions, yet demonstrated a complete absence of an association with the dense LDL fractions. In contrast, HL was positively correlated with the dense LDL fractions but showed no association with buoyant LDL. LPL was also positively correlated with several buoyant LDL fractions; however, the correlations were weaker than those of PLTP. PLTP and LPL were positively correlated and HL was negatively correlated with HDL fractions.The results suggest that PLTP and HL may be important and independent determinants of the LDL subpopulation density distributions.

scholarly journals Disruption of Phospholipid Transfer Protein–Mediated High-Density Lipoprotein Maturation Reduces Scavenger Receptor BI Deficiency–Driven Atherosclerosis Susceptibility Despite Unexpected Metabolic Complications

2020 ◽  
Vol 40 (3) ◽  
pp. 611-623 ◽  
Author(s):  
Menno Hoekstra ◽  
Ronald J. van der Sluis ◽  
Reeni B. Hildebrand ◽  
Bart Lammers ◽  
Ying Zhao ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Knockout Mice ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Phospholipid Transfer Protein ◽  
Double Knockout ◽  
Metabolic Complications ◽  
Scavenger Receptor Bi ◽  
Transfer Protein ◽  
Phospholipid Transfer

Objective: We tested the hypothesis that enlarged, dysfunctional HDL (high-density lipoprotein) particles contribute to the augmented atherosclerosis susceptibility associated with SR-BI (scavenger receptor BI) deficiency in mice. Approach and Results: We eliminated the ability of HDL particles to fully mature by targeting PLTP (phospholipid transfer protein) functionality. Particle size of the HDL population was almost fully normalized in male and female SR-BI×PLTP double knockout mice. In contrast, the plasma unesterified cholesterol to cholesteryl ester ratio remained elevated. The PLTP deficiency-induced reduction in HDL size in SR-BI knockout mice resulted in a normalized aortic tissue oxidative stress status on Western-type diet. Atherosclerosis susceptibility was—however—only partially reversed in double knockout mice, which can likely be attributed to the fact that they developed a metabolic syndrome-like phenotype characterized by obesity, hypertriglyceridemia, and a reduced glucose tolerance. Mechanistic studies in chow diet–fed mice revealed that the diminished glucose tolerance was probably secondary to the exaggerated postprandial triglyceride response. The absence of PLTP did not affect LPL (lipoprotein lipase)-mediated triglyceride lipolysis but rather modified the ability of VLDL (very low-density lipoprotein)/chylomicron remnants to be cleared from the circulation by the liver through receptors other than SR-BI. As a result, livers of double knockout mice only cleared 26% of the fractional dose of [ 14 C]cholesteryl oleate after intravenous VLDL-like particle injection. Conclusions: We have shown that disruption of PLTP-mediated HDL maturation reduces SR-BI deficiency-driven atherosclerosis susceptibility in mice despite the induction of proatherogenic metabolic complications in the double knockout mice.

scholarly journals The mechanism of human plasma phospholipid transfer protein-induced enlargement of high-density lipoprotein particles: evidence for particle fusion

1996 ◽  
Vol 313 (1) ◽  
pp. 275-282 ◽  
Author(s):  
Sari LUSA ◽  
Matti JAUHIAINEN ◽  
Jari METSO ◽  
Pentti SOMERHARJU ◽  
Christian EHNHOLM
Keyword(s):  
Particle Size ◽  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Density ◽  
Rapid Decline ◽  
Phospholipid Transfer Protein ◽  
Surface Lipid ◽  
Transfer Protein ◽  
Large Particles ◽  
Phospholipid Transfer

1. Phospholipid transfer protein (PLTP) mediates conversion of high-density lipoprotein (HDL3) to large particles, with concomitant release of apolipoprotein A-I (apoA-I). To study the mechanisms involved in this conversion, reconstituted HDL (rHDL) particles containing either fluorescent pyrenylacyl cholesterol ester (PyrCE) in their core (PyrCE-rHDL) or pyrenylacyl phosphatidylcholine (PyrPC) in their surface lipid layer (PyrPC-rHDL) were prepared. Upon incubation with PLTP they behaved as native HDL3, in that their size increased considerably. 2. When PyrPC-rHDL was incubated with HDL3 in the presence of PLTP, a rapid decline of the pyrene excimer/monomer fluorescence ratio (E/M) occurred, demonstrating that PLTP induced mixing of the surface lipids of PyrPC-rHDL and HDL3. As this mixing was almost complete before any significant increase in HDL particle size was observed, it represents PLTP-mediated phospholipid transfer or exchange that is not directly coupled to the formation of large HDL particles. 3. When core-labelled PyrCE-rHDL was incubated in the presence of PLTP, a much slower, time-dependent decrease of E/M was observed, demonstrating that PLTP also promotes mixing of the core lipids. The rate and extent of mixing of core lipids correlated with the amount of PLTP added and with the increase in particle size. The enlarged particles formed could be visualized as discrete, non-aggregated particles by electron microscopy. Concomitantly with the appearance of enlarged particles, lipid-poor apoA-I molecules were released. These data, together with the fact that PLTP has been shown not to mediate transfer of cholesterol esters, strongly suggest that particle fusion rather than (net) lipid transfer or particle aggregation is responsible for the enlargement of HDL particles observed upon incubation with PLTP. 4. ApoA-I rHDL, but not apoA-II rHDL, were converted into large particles, suggesting that the presence of apoA-I is required for PLTP-mediated HDL fusion. A model for PLTP-mediated enlargement of HDL particles is presented.

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