Dysregulated Lipid Transport Proteins Correlate With Pathogenesis and Outcome in Severe Alcoholic Hepatitis

Maras, Jaswinder Singh; Das, Subodh K.; Bhat, Adil; Vyas, Ashish Kumar; Chaudhary, Sudrishti; Sukriti, Sukriti; Gupta, Abhishak; Bihari, Chagan; Mahiwall, Rakhi; Sarin, Shiv Kumar

doi:10.1002/hep4.1438

Cited by 7 publications

(13 citation statements)

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“…Patients manifesting severe alcoholic hepatitis, inflammation and oxidative stress symptoms had a correlation with a decrease of circulating paroxanase/arylesterase 1 (PON1) in the blood and stimulated alternatively activated (M2) macrophages through activation of CD36. The idea here is that activated macrophages internalize increased amounts of oxLDLs via CD36 and SRA1 and that contributes to the pathophysiology of severe alcoholic hepatitis (Maras et al, 2019). However, none of the studies have documented the contribution of SR-B1 or CD36 expressed on LSECs in maintaining a homeostatic environment in the liver or a modulation in their expression in various diseases.…”

Section: Scavenger Receptor B (Sr-b)mentioning

confidence: 99%

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

2020

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Liver sinusoidal endothelial cells (LSECs) are the most abundant non-parenchymal cells lining the sinusoidal capillaries of the hepatic system. LSECs are characterized with numerous fenestrae and lack basement membrane as well as a diaphragm. These unique morphological characteristics of LSECs makes them the most permeable endothelial cells of the mammalian vasculature and aid in regulating flow of macromolecules and small lipid-based structures between sinusoidal blood and parenchymal cells. LSECs have a very high endocytic capacity aided by scavenger receptors (SR), such as SR-A, SR-B (SR-B1 and CD-36), SR-E (Lox-1 and mannose receptors), and SR-H (Stabilins). Other high-affinity receptors for mediating endocytosis include the FcγRIIb, which assist in the antibody-mediated removal of immune complexes. Complemented with intense lysosomal activity, LSECs play a vital role in the uptake and degradation of many blood borne waste macromolecules and small (<280 nm) colloids. Currently, seven Toll-like receptors have been investigated in LSECs, which are involved in the recognition and clearance of pathogen-associated molecular pattern (PAMPs) as well as damage associated molecular pattern (DAMP). Along with other SRs, LSECs play an essential role in maintaining lipid homeostasis with the lowdensity lipoprotein receptor-related protein-1 (LRP-1), in juxtaposition with hepatocytes. LSECs co-express two surface lectins called L-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin Receptor (L-SIGN) and liver sinusoidal endothelial cell lectin (LSECtin). LSECs also express several adhesion molecules which are involved in the recruitment of leukocytes at the site of inflammation. Here, we review these cell surface receptors as well as other components expressed by LSECs and their functions in the maintenance of liver homeostasis. We further discuss receptor expression and activity and dysregulation associated with the initiation and progression of many liver diseases, such as hepatocellular carcinoma, liver fibrosis, and cirrhosis, alcoholic and non-alcoholic fatty liver diseases and pseudocapillarization with aging.

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Section: Scavenger Receptor B (Sr-b)mentioning

confidence: 99%

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

2020

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“…Apolipoprotein C-3 stimulates monocytes, promotes tissue damage (41), and promotes the formation and outcome of alcoholic cirrhosis. Besides, it increases the risk of Alzheimer's disease by increasing high-density lipoprotein (HDL) (42,43). Apolipoprotein C-4 increases the risk of diabetes in young people and affects the lipid profile of patients (44).…”

Section: Discussionmentioning

confidence: 99%

Investigation of Specific Proteins Related to Different Types of Coronary Atherosclerosis

Meng

Ruan

Chen

et al. 2021

Front. Cardiovasc. Med.

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Objective: Coronary heart disease (CHD) is a complex disease caused by multifaceted interaction between genetic and environmental factors, which makes identification of the most likely disease candidate proteins and their associated risk markers a big challenge. Atherosclerosis is presented by a broad spectrum of heart diseases, including stable coronary artery disease (SCAD) and acute myocardial infarction (AMI), which is the progressive stage of SCAD. As such, the correct and prompt diagnosis of atherosclerosis turns into imperative for precise and prompt disease diagnosis, treatment and prognosis.Methods: The current work aims to look for specific protein markers for differential diagnosis of coronary atherosclerosis. Thirty male patients between 45 and 55 years diagnosed with atherosclerosis were analyzed by tandem mass tag (TMT) mass spectrometry. The study excluded those who were additionally diagnosed with hypertension and type 1 and 2 diabetes. The Mufuzz analysis was applied to select target proteins for precise and prompt diagnosis of atherosclerosis, most of which were most related to high lipid metabolism. The parallel reaction monitoring (PRM) was used to verify the selected target proteins. Finally, The receiver operating characteristic curve (ROC) was calculated by a random forest experiment.Results: One thousand one hundred and forty seven proteins were identified in the TMT mass spectrometry, 907 of which were quantifiable. In the PRM study, six proteins related to lipid metabolism pathway were selected for verification and they were ALB, SHBG, APOC2, APOC3, APOC4, SAA4.Conclusion: Through the detected specific changes in these six proteins, our results provide accuracy in atherosclerosis patients' diagnosis, especially in cases with varying types of the disease.

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“…Another study reported PON1 in patients with biopsy-proven severe alcoholic hepatitis (n = 20) and in an unreported number of healthy controls [16 ]. Low plasma PON1 levels were inversely correlated with the severity of alcoholic hepatitis and termed a predictor of survival (28-day mortality).…”

Section: Proteins Related To Lipid Metabolismmentioning

confidence: 98%

“…One study analyzed the plasma proteomic profiles of patients with alcoholic cirrhosis [16 ] and four studies evaluated plasma and liver tissue from animals with ALD [17][18][19][20] ].…”

Section: Studies On Aldmentioning

confidence: 99%

“…histologically verified severe alcoholic hepatitis and controls (number not reported) without evidence of liver disease (methods of assessment not reported) [16 ]. After performing MS-based proteomics on the subjects' blood, Paraoxonase-1 was left as the candidate biomarker and highlighted in the study.…”

Section: Maras Et Al Analyzed the Plasma Proteome Of Twenty Patients Withmentioning

confidence: 99%

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Mass Spectrometry-Based Proteomics in Alcoholic and Non-Alcoholic Steatohepatitis

Le¹,

Kimer²,

Gluud³

2021

JJGH

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1.1. Aims: This review aims to provide an overview of candidate biomarkers derived from MS-based proteomics representing inflammation or fibrosis in NAFLD and ALD. The prevalence of non-alcoholic fatty liver disease (NAFLD) and Alcoholic Liver Disease (ALD) is increasing worldwide and the associated morbidity and mortality is considerable. Both conditions are characterized by increasing steatosis, inflammation, and fibrosis. Accurate, non-invasive biomarkers are needed to ensure earlier diagnosis and intervention. Mass-spectrometry (MS)-based proteomics is a leading technology within biomarker identification. Methods:We identified nine papers describing relevant MSbased analyses of NAFLD and ALD. Results: The studies described potential biomarkers including serum Paraoxonase-1 (PON1), clusterin, lumican and Polymeric Immunoglobulin Receptor (PIGR). The combined evidence suggested that the concentration of PON1, which is an enzyme with anti-inflammatory and anti-atherogenic properties, was lower in patients with NAFLD of all stages, which correlates with previous research on NAFLD and other metabolic diseases. PIGR was upregulated in plasma in ALD and NAFLD but downregulated in the liver in NAFLD. The protein plays a role in mucosal immunity, but its association to NAFLD is not well known. Lumican is a proteoglycan associated with the formation of fibrosis. It was upregulated in plasma from patients with NASH and advanced fibrosis as well as patients with alcoholic hepatitis. Clusterin has pro-tective anti-fibrotic and anti-steatotic effects and was upregulated in liver and plasma from animal models with NAFLD and ALD fibrosis. Conclusion:There may be proteins common to the inflammation or fibrotic pathway between the two diseases alcoholic and non-alcoholic steatohepatitis.

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Dysregulated Lipid Transport Proteins Correlate With Pathogenesis and Outcome in Severe Alcoholic Hepatitis

Cited by 7 publications

References 54 publications

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

Prominent Receptors of Liver Sinusoidal Endothelial Cells in Liver Homeostasis and Disease

Investigation of Specific Proteins Related to Different Types of Coronary Atherosclerosis

Mass Spectrometry-Based Proteomics in Alcoholic and Non-Alcoholic Steatohepatitis

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