Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enterically derived high-density lipoprotein restrains liver injury through the portal vein.

ABSTRACT: The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis also occurs in the small intestine. Here, we show that intestine-derived HDL traverses the portal vein in the HDL₃ subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL₃, but not HDL₂ or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and instead supported extracellular inactivation of LPS. In mouse models involving surgical, dietary, or alcoholic intestinal insult, loss of intestine-derived HDL worsened liver injury, whereas outcomes were improved by therapeutics that elevated and depended upon raising intestinal HDL. Thus, protection of the liver from injury in response to gut-derived LPS is a major function of intestinally synthesized HDL.

SUBMITTER: Han YH

PROVIDER: S-EPMC8478306 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Enterically derived high density lipoprotein restrains liver injury via the portal vein

Project description:The proteomes of HDL subspecies, HDL2 and HDL3, from pooled human serum purified by density gradient centrifugation were generated and compared to the proteomes of HDL2 and HDL3 derived from tportal venouhe s and antecubital venous blood matched across these two locations from the same individual. The latter were purified by size exclusion chromatography coupled with immunoprecipitation with anti-apoA1 mAb.

2021-04-27 | MSV000087310 | MassIVE

Liver-specific phospholipid transfer protein deficiency reduces high-density lipoprotein and non-high-density lipoprotein production in mice.

Project description:The liver is one of the critical organs for lipoprotein metabolism and a major source for phospholipid transfer protein (PLTP) expression. The effect of liver-specific PLTP deficiency on plasma lipoprotein production and metabolism in mice was investigated.We created a liver-specific PLTP-deficient mouse model. We measured plasma high-density lipoprotein (HDL) and apolipoprotein B (apoB)-containing lipoprotein (or non-HDL) levels and their production rates. We found that hepatic ablation of PLTP leads to a significant decrease in plasma PLTP activity, HDL lipids, non-HDL lipids, apoAI, and apoB levels. In addition, nuclear magnetic resonance examination of lipoproteins showed that the deficiency decreases HDL and apoB-containing lipoprotein particle numbers, as well as very low-density lipoprotein particle size, which was confirmed by electron microscopy. Moreover, HDL particles from the deficient mice are lipid-poor ones. To unravel the mechanism, we evaluated the apoB and triglyceride production rates. We found that hepatic PLTP deficiency significantly decreases apoB and triglyceride secretion rates. To investigate the role of liver PLTP on HDL production, we set up primary hepatocyte culture studies and found that the PLTP-deficient hepatocytes produce less nascent HDL. Furthermore, we found that exogenous PLTP promotes nascent HDL production through an ATP-binding cassette A 1-mediated pathway.Liver-specific PLTP deficiency significantly reduces plasma HDL and apoB-containing lipoprotein levels. Reduction of production rates of both particles is one of the mechanisms.

| S-EPMC4263421 | biostudies-literature

Liver disease alters high-density lipoprotein composition, metabolism and function.

Project description:High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

| S-EPMC5542032 | biostudies-literature

Development of a Model to Predict Portal Vein Thrombosis in Liver Transplant Candidates: The Portal Vein Thrombosis Risk Index.

Project description:Portal vein thrombosis (PVT) is associated with inferior pretransplantation and posttransplantation outcomes. We aimed to create a predictive model to risk stratify transplant candidates for PVT. Data on adult transplants in the United States during the Model for End-Stage Liver Disease (MELD) era through September 2016 were reviewed. We constructed and validated a scoring system composed of routine, readily available clinical information to predict the development of incident PVT at 12 months from transplantation listing. A total of 66,568 liver transplant candidates were dichotomized into 2 groups to construct (n = 34,751) and validate (n = 31,817) a scoring system. In general, the derivation and validation cohorts were clinically similar. Although nonalcoholic steatohepatitis was a significant predictor of incident PVT (hazard ratio, 1.29; 95% confidence interval, 1.08-1.54; P < 0.001), age, MELD score, and moderate-to-severe ascites were also associated with increased risk. African American race was associated with decreased risk. A scoring system (PVT risk index [RI]) of these 5 variables had an area under the curve of 0.71 and 0.70 in both derivation and validation cohorts, respectively. By applying the low cutoff score of 2.6, incident PVT could be accurately excluded (negative predictive value 94%). Using the high cutoff score of 4.6 (positive predictive value 85%), PVT could be diagnosed with high accuracy. The PVT-RI predicts which candidates awaiting lifesaving liver transplantation will and will not develop future PVT. Although this scoring system will require prospective validation, it provides a powerful new tool for the clinician when risk stratifying cirrhosis patients prior to liver transplantation for future PVT development.

| S-EPMC6864229 | biostudies-literature

High Density Lipoprotein Proteome in Non-alcoholic Fatty Liver Disease Patients

Project description:Characterization of HDL proteome in patients diagnosed with non-alcoholic fatty liver disease and to evaluate the impact on HDL function.

2018-09-13 | PXD005847 | Pride

Simultaneous portal and hepatic vein embolization before major liver resection.

Project description:BackgroundRegenerative liver surgery expands the limitations of technical resectability by increasing the future liver remnant (FLR) volume before extended resections in order to avoid posthepatectomy liver failure (PHLF). Portal vein rerouting with ligation of one branch of the portal vein bifurcation (PVL) or embolization (PVE) leads to a moderate liver volume increase over several weeks with a clinical dropout rate of 20-40%, mostly due to tumor progression during the waiting period. Accelerated liver regeneration by the Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) was poised to overcome this limitation by reduction of the waiting time, but failed due increased perioperative complications. Simultaneous portal and hepatic vein embolization (PVE/HVE) is a novel minimal invasive way to induce rapid liver growth without the need of two surgeries.PurposeThis article summarizes published results of PVE/HVE and analyzes what is known about its efficacy to achieve resection, safety, and the volume changes induced.ConclusionsPVE/HVE holds promise to induce accelerated liver regeneration in a similar safety profile to PVE. The demonstrated accelerated hypertrophy may increase resectability. Randomized trials will have to compare PVE/HVE and PVE to determine if PVE/HVE is superior to PVE.

| S-EPMC8370912 | biostudies-literature

Nontumoral Portal Vein Thrombosis: A Challenging Consequence of Liver Cirrhosis.

Project description:Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis.

| S-EPMC7782107 | biostudies-literature

The difference of microRNA profiles among control, normal high density lipoprotein-treated and proflammatory high density lipoprotein-treated endothelial cells

Project description:The potential mechanism were successfully illustrated through detecting different expression of microRNAs in between proinflammatory high density lipprotein (pHDL), nomal high density lipprotein (nHDL) and control group, to study whether microRNAs play important roles in the endothelial dysfunction caused by pHDL.

2020-08-31 | GSE156800 | GEO

Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy.

Project description:This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18?mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), ?-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P < 0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

| S-EPMC6231388 | biostudies-other

High-density lipoprotein cholesterol concentration and acute kidney injury after noncardiac surgery.

Project description:BackgroundAbnormal High-density Lipoprotein Cholesterol Concentration is closely related to postoperative acute kidney injury (AKI) after cardiac surgeries. The purpose of this study was to analyze the relationship between High-density Lipoprotein Cholesterol Concentration and acute kidney injury after non-cardiac surgeries.MethodThis was a single-center cohort study for elective non-cardiac non-kidney surgery from January 1, 2012, to December 31, 2017. The endpoint was the occurrence of acute kidney injury (AKI) 7?days postoperatively in the hospital. Preoperative serum High-density Lipoprotein Cholesterol Concentration was examined by multivariate logistic regression models before and after propensity score weighting analysis.ResultsOf the 74,284 surgeries, 4.4% (3159 cases) suffered acute kidney injury. The odds ratio for HDL (0.96-1.14 as reference, <?0.96, 1.14-1.35, >?1.35) was 1.28 (1.14-1.41), P?<?0.001; 0.91 (0.80-1.03), P?=?0.150; 0.75 (0.64-0.85), P?<?0.001, respectively. Using a dichotomized cutoff point for propensity analysis, Preoperative serum HDL?<? 1.03?mmol/L (>?1.03 as reference) was associated with increased risk of postoperative AKI, with odds ratio 1.40 (1.27?~?1.52), P?<?0.001 before propensity score weighting, and 1.32 (1.21-1.46), P?<?0.001 after propensity score weighting. Sensitivity analysis with other cut values of HDL showed similar results.ConclusionsUsing multivariate regression analyses before and after propensity score weighting, in addition to multiple sensitivity analysis methods, this study found that following non-cardiac surgery, low HDL cholesterol levels were independent risk factors for AKI.

| S-EPMC7183648 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data