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Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III.

The hypolipidemic effect exerted by beta,beta'-tetramethyl-hexadecanedioic acid (Medica 16) is accounted for by enhanced catabolism of plasma triglyceride-rich lipoproteins due to a decrease in plasma apolipoprotein C-III (Frenkel, B., Mayorek, N., Hertz, R., and Bar-Tana, J. (1988) J. Biol. Chem. 263, 8491-8497; Frenkel, B., Bishara-Shieban, J., and Bar-Tana, J. (1994) Biochem. J. 298, 409-414). Decrease in apolipoprotein C-III exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates (e.g. Medica 16, fibrate drugs) is shown here to result from suppression of apolipoprotein C…

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk.

AIMS: Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200-500 mg/dL (2.26-5.65 mmol/L). Patients received olezarsen (10…

Определение аполипротеина С-III в качестве потенциального плазматического биомаркера, связанного с разрешением вируса гепатита С.

Понимание взаимодействия между вирусом и призраком, которое приводит к тому, что около 20% пациентов с острым вирусом гепатита С (ГХВ) получают вирусную терапию, вероятно, является ключом к разработке более эффективных стратегий лечения и профилактики. Острая гепатит С инфекция, как правило, носит асимптомический характер и поэтому редко диагностируется. Тем не менее, в ходе анализа HCV нуклеиновая кислота, проведенного на всех пожертвованиях крови, обнаруживаются доноры, которые урегулировали инфекцию HCV после сероконверсии. Здесь мы использовали технологию SELDI-TOF-MS для сопоставления на

Совпадение в аннотации оригинала
Understanding the virus-host interactions that lead to approximately 20% of patients with acute Hepatitis C Virus (HCV) infection to viral c … n the three groups. After purification we identified by nanoLC-Q-TOF-MS/MS this candidate marker as Apolipoprotein C-III (ApoC-III). The identification was confirmed by western blot analysis. Levels of ApoC-III were then determined in the 45 plasma samples by immunoturbidimetric assay. ApoC-III was found to be higher in donors who had resolved their HCV infection than …

Triglyceride-independent associations between circulating levels of apolipoprotein C-III and biomarkers of inflammation.

BACKGROUNDS AND AIMS: Preclinical studies suggest that a triglyceride (TG)-independent proinflammatory action of apolipoprotein C-III (apoCIII) exists. We aimed to investigate the relationship between circulating apoCIII levels and subclinical inflammation markers across different cohorts with distinctive inflammatory patterns: patients with metabolic disorders (MDs), patients with rheumatoid arthritis (RA), and controls. Specifically, we assessed the associations of apoCIII with acute inflammation biomarkers (e.g., high sensitivity C-reactive protein (hsCRP)) and novel systemic inflammation b…

Low-density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease.

BACKGROUND: Low-density lipoprotein (LDL) that contains apolipoprotein (apo) C-III makes up only 10% to 20% of plasma LDL but has a markedly altered metabolism and proatherogenic effects on vascular cells. METHODS AND RESULTS: We examined the association between plasma LDL with apoC-III and coronary heart disease in 320 women and 419 men initially free of cardiovascular disease who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow-up and matched controls who remained free of coronary heart disease. Concentrations of LDL with apoC-III (measured as apoB in this

Hypertriglyceridaemia associated with an abnormal triglyceride-rich lipoprotein carrying excess apolipoprotein C-III-2.

Two men aged 48 and 35 years with severe hypertriglyceridaemia, glucose intolerance, and a secondary anaemia had more apolipoprotein C-III-2 and less apo C-III-1 on their triglyceride-rich lipoproteins (d less than 1.006) than did types IV or V lipaemic controls. Although the patients' abnormal lipoproteins seemed to produce normal activation of lipoprotein lipase, they did not serve as an efficient substrate for purified lipoprotein lipase. Adipose tissue of case 1 had considerable lipoprotein-lipase activity and the hypertriglyceridaemia responded to dietary therapy (carbohydrate 180 g, fat …

Apolipoprotein C-III inhibitors for the treatment of hypertriglyceridemia: a meta-analysis of randomized controlled trials.

INTRODUCTION: Hypertriglyceridemia is related to atherosclerotic cardiovascular risk and pancreatitis risk. The efficacy and safety of apolipoprotein C-III (APOC-III) inhibitors remains unclear. AIM: To investigate the effects of APOC-III inhibitors on hypertriglyceridemia and its complications. METHODS: We systematically searched PubMed, Embase, and Cochrane Central databases from inception to May 2024 for randomized controlled trials (RCTs) comparing APOC-III inhibitors to placebo in patients with hypertriglyceridemia. We pooled percentage standardized mean difference (SMD) changes and ris…

Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation.

Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein … nformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are …

Deoxyribonucleic acid polymorphism in the apolipoprotein A-1-C-III gene cluster. Association with hypertriglyceridemia.

A DNA sequence polymorphism, revealed by digestion of human DNA with the restriction endonuclease Sst-1 and hybridization with an apolipoprotein A-I complementary DNA clone, has been shown to be located in or close to the 3' noncoding region of the apolipoprotein C-III gene. This polymorphism is found in significantly increased prevalence (P less than 0.001) in Caucasian hypertriglyceridemic subjects compared with race-matched controls, and its distribution in normal individuals of differing racial origins is reported. Furthermore, no alteration of high density lipoprotein or apolipoprotein A-…

Metabolism of apolipoproteins C-II, C-III, and B in hypertriglyceridemic men. Changes after heparin-induced lipolysis.

The C apolipoproteins are normally transferred to high density lipoproteins (HDL) after lipolysis of very low density lipoprotein (VLDL) triglyceride. In previous studies, a loss of plasma C apolipoproteins was documented after heparin-induced lipolysis in hypertriglyceridemic subjects. The present studies were designed to determine if this decline in plasma C apolipoproteins was due to their clearance with VLDL remnants. Five Type IV hypertriglyceridemic and two normal subjects were injected with 125I-VLDL and 131I-low density lipoproteins (LDL) to document kinetically an excess of VLDL apoli

Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans.

BACKGROUND: Olezarsen is a GalNAc3-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans. METHODS: A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 w…

Targeting Apolipoprotein C-III for the Management of Severe Hypertriglyceridemia: Current Research and Future Directions.

Hypertriglyceridemia is characterized by elevated triglyceride levels in the blood, which increases the risk of cardiovascular disease and pancreatitis. This condition stems from multiple factors including lifestyle choices, genetics, and conditions such as diabetes and metabolic syndrome. Apolipoprotein C-III (APOC3), a protein for lipid metabolism, hinders enzymes necessary for breaking down triglycerides and thus plays a key role in hypertriglyceridemia. Variations in the APOC3 gene are associated with varying triglyceride levels among individuals. Recent genetic studies and clinical trials…

Effects of nicotinic acid on concentrations of serum apolipoproteins B, C-I, C-II, C-III and E in hyperlipidemic patients.

Twenty-four patients with Type IIa, IIb, III and IV hyperlipoproteinemia (HLP) were treated with 4 g of nicotinic acid daily with the purpose to study its effect on serum apolipoprotein B, C-I, C-II, C-III and E concentrations. Triglyceride and total cholesterol concentrations of whole serum and of different serum lipoprotein fractions were also determined. Analyses were performed prior to and after a drug treatment period of 6 weeks, during which all the patients were weight stable. Treatment caused a decrease in serum concentrations of apolipoproteins C-I, C-II, C-III and E. These highly sig

[Apolipoprotein C III gene Sst I polymorphism in patients with endogenous hypertriglyceridemia in Chinese population].

OBJECTIVE: To investigate the apoC III gene Sst I polymorphism and its relationship with serum lipids and apolipoproteins (apo) levels in patients with endogenous hypertriglyceridemia in Chinese population. METHODS: The genotype and allele frequency of apoC III gene Sst I polymorphism was assayed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Serum lipids were measured by enzymatic kits and apolipoproteins A I, A II, B100, C II, C III and E were measured by RID kits developed by Apolipoprotein Research Unit of WCUMS in 176 HTG patients whose fasting serum

Apolipoprotein C-III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria.

OBJECTIVES: We studied apolipoprotein C-III (apoC-III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes. METHODS: The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries. RESULTS: ApoC-III predicted D…

D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile.

Apolipoprotein C-III deficiency provides cardiovascular protection, but apolipoprotein C-III is not known to be associated with human amyloidosis. Here we report a form of amyloidosis characterized by renal insufficiency caused by a new apolipoprotein C-III variant, D25V. Despite their uremic state, the D25V-carriers exhibit low triglyceride (TG) and apolipoprotein C-III levels, and low very-low-density lipoprotein (VLDL)/high high-density lipoprotein (HDL) profile. Amyloid fibrils comprise the D25V-variant only, showing that wild-type apolipoprotein C-III does not contribute to amyloid deposi…

Transferrin and apolipoprotein C-III isofocusing are complementary in the diagnosis of N- and O-glycan biosynthesis defects.

BACKGROUND: Apolipoprotein C-III (apoC-III) isoelectric focusing (IEF) can be used to detect abnormalities in the biosynthesis of core 1 mucin-type O-glycans. METHODS: We studied plasma samples from 55 patients with various primary defects in N- and/or O-glycosylation, 21 patients with secondary N-glycosylation defects, and 6 patients with possible glycosylation abnormalities. Furthermore, we analyzed 500 plasma samples that were sent to our laboratory for selective screening for inborn errors of metabolism. RESULTS: Plasma samples from patients with congenital disorders of glycosylation (CD…

Concentrations of apolipoprotein C-III in healthy cows during the peripartum period and cows with milk fever.

Apolipoprotein (apo) C-III is a low-molecular-mass protein mainly distributed in the high-density lipoprotein fraction in cattle serum. We have recently shown that the apoC-III concentration is decreased in cows with fatty liver, ketosis, left displacement of the abomasum, retained placenta and milk fever. The decrease was most distinct in milk fever, thereby suggesting that apoC-III is particularly relevant to the development of milk fever and also that apoC-III is a candidate diagnostic marker for this disease. The purpose of the present study was to examine whether the apoC-III concentratio

[An Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum ins…

Recent advances in treating hypertriglyceridemia in patients at high risk of cardiovascular disease with apolipoprotein C-III inhibitors.

INTRODUCTION: Mild-to-moderate hypertriglyceridemia (HTG) is commonly encountered and is associated with atherosclerotic cardiovascular dise … apies that reduce TG levels via apo C-III inhibition. The PubMed database was searched using terms: apolipoprotein C-III, ARO-APOC3, atherosclerotic cardiovascular disease, olezarsen, triglycerides, and volanesorsen; study types: clinical trials, systematic reviews, and meta-analyses; and time criterion 2005 to present. EXPERT OPINION: Apo C-III inhibition is a promi …