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Allyson M Morton, Manja Koch, Carlos O Mendivil, Jeremy D Furtado, Anne Tjønneland, Kim Overvad, Liyun Wang, Majken K Jensen, Frank M Sacks
BACKGROUND: Subspecies of HDL contain apolipoprotein E (apoE) and/or apoCIII. Both proteins have properties that could affect HDL metabolism. The relation between HDL metabolism and risk of coronary heart disease (CHD) is not well understood. METHODS: Eighteen participants were given a bolus infusion of [D3]L-leucine to label endogenous proteins on HDL. HDL was separated into subspecies containing apoE and/or apoCIII and then into 4 sizes. Metabolic rates for apoA-I in HDL subspecies and sizes were determined by interactive modeling...
February 22, 2018: JCI Insight
I Ramasamy
The role of the clinical laboratory is evolving to provide more information to clinicians to assess cardiovascular disease (CVD) risk and target therapy more effectively. Current routine methods to measure LDL-cholesterol (LDL-C), the Friedewald calculation, ultracentrifugation, electrophoresis and homogeneous direct methods have established limitations. Studies suggest that LDL and HDL size or particle concentration are alternative methods to predict future CVD risk. At this time there is no consensus role for lipoprotein particle or subclasses in CVD risk assessment...
January 11, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Eiichi Araki, Shizuya Yamashita, Hidenori Arai, Koutaro Yokote, Jo Satoh, Toyoshi Inoguchi, Jiro Nakamura, Hiroshi Maegawa, Narihito Yoshioka, Yukio Tanizawa, Hirotaka Watada, Hideki Suganami, Shun Ishibashi
OBJECTIVE: Type 2 diabetes is frequently complicated with atherogenic dyslipidemia. This study aimed to evaluate the efficacy and safety of pemafibrate (K-877) in patients with type 2 diabetes comorbid with hypertriglyceridemia. RESEARCH DESIGN AND METHODS: Patients were randomly assigned to three groups and received placebo (n = 57), 0.2 mg/day pemafibrate (n = 54), or 0.4 mg/day pemafibrate (n = 55) for 24 weeks (treatment period 1). Subsequently, the patients received follow-up treatment for another 28 weeks (treatment period 2), in which the placebo was switched to 0...
January 3, 2018: Diabetes Care
Minzeng Sun, Lin Chen, Hui Liu, Lihui Ma, Tiansong Wang, Yueli Liu
BACKGROUND: The SstI polymorphism in the apolipoprotein 3 gene (apoC3) has been identified in many ethnic groups. In addition, the S2 allele of the SstI polymorphism is shown to be associated with increased plasma triglyceride (TG) levels. Plasma apoCIII is an important atherogenic factor, which interrupts lipid metabolism and is positively associated with plasma TG levels. However, the existence of the SstI polymorphism in the Li ethnic group in China remains to be confirmed. The relationship between the S2 allele of the SstI polymorphism and plasma apoCIII or TG and their roles in atherosclerosis are also unknown...
November 21, 2017: Lipids in Health and Disease
Natalia A Rocha, Cara East, Jun Zhang, Peter A McCullough
PURPOSE OF REVIEW: Apolipoprotein CIII (ApoCIII) is now recognized as a key regulator in severe hypertriglyceridemia, chylomicronemia, and conditions of triglyceride-rich lipoprotein (TRL) remnant excess due to its inhibition of lipoprotein lipase (LPL) and hepatic lipase, leading to decreased hepatic reuptake of TRLs, as well as enhanced synthesis and secretion of VLDL from the liver. ApoCIII gain-of-function mutations are associated with atherosclerosis and coronary heart disease (CHD), and contribute to the development of cardiometabolic syndrome, hypertriglyceridemia, and type 2 diabetes mellitus...
November 9, 2017: Current Atherosclerosis Reports
Yuan Yue, Hao Jiang, Shouqing Yan, Yao Fu, Chang Liu, Xulei Sun, Menglong Chai, Yan Gao, Bao Yuan, Chengzhen Chen, Lisheng Dai, Jiabao Zhang, Yu Ding
Apolipoprotein CIII (ApoCIII) has been shown to be associated with the inflammatory response, but the mechanism of its inflammatory effects remains unclear. Because vascular endothelial cells (VECs) play a key role in the development of inflammation, the present study was performed to investigate inflammatory mechanisms induced by ApoCIII in VECs. In this study, we screened differentially expressed genes (DEGs) using RNA-sequencing. The results identified 390 up-regulated genes and 257 down-regulated genes...
September 21, 2017: Cell Cycle
Gaia Botteri, Marta Montori, Anna Gumà, Javier Pizarro, Lídia Cedó, Joan Carles Escolà-Gil, Diana Li, Emma Barroso, Xavier Palomer, Alison B Kohan, Manuel Vázquez-Carrera
AIM/HYPOTHESIS: Here, our aim was to examine whether VLDL and apolipoprotein (apo) CIII induce endoplasmic reticulum (ER) stress, inflammation and insulin resistance in skeletal muscle. METHODS: Studies were conducted in mouse C2C12 myotubes, isolated skeletal muscle and skeletal muscle from transgenic mice overexpressing apoCIII. RESULTS: C2C12 myotubes exposed to VLDL showed increased levels of ER stress and inflammatory markers whereas peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and AMP-activated protein kinase (AMPK) levels were reduced and the insulin signalling pathway was attenuated...
November 2017: Diabetologia
Congye Wu, Lei Zou, Shujing Shi, Zhihui Tong, Xiao Shen, Dongliang Yang, Lu Ke, Weiqin Li, Jieshou Li
OBJECTIVE: The aim of this study was to investigate the role of hypertriglyceridemia for acute kidney injury (AKI) in the course of acute pancreatitis. METHODS: Patients with acute pancreatitis were retrospectively divided into four groups according to admission triglyceride: normal group, mild HTG group, moderate HTG group and severe HTG group. Clinical characteristics were compared among these groups. Wild type (WT) mice and Human ApoC III transgenic (ApoCIIItg) mice were used in the next animal experiments...
July 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Pier Luigi Calvo, Marco Spada, Ivana Rabbone, Michele Pinon, Francesco Porta, Fabio Cisarò, Stefania Reggiani, Angelo B Cefalù, Luisella Sturiale, Domenico Garozzo, Dirk J Lefeber, Jaak Jaeken
We report on a 12-year-old adopted boy with psychomotor disability, absence seizures, and normal brain MRI. He showed increased (but initially, at 5 months, normal) serum cholesterol, increased alkaline phosphatases, transiently increased transaminases and hypoceruloplasminemia with normal serum and urinary copper. Blood levels of immunoglobulins, haptoglobin, antithrombin, and factor XI were normal. A type 2 serum transferrin isoelectrofocusing and hypoglycosylation of apoCIII pointed to a combined N- and O-glycosylation defect...
June 23, 2017: JIMD Reports
Mengdie Luo, Aiying Liu, Shuai Wang, Tianle Wang, Die Hu, Sha Wu, Daoquan Peng
Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIIIHDL) and HDL-mediated cholesterol efflux...
May 24, 2017: Scientific Reports
Himanshu Rai, Nakul Sinha, James Finn, Suraksha Agrawal, Sarabjit Mastana
Genetic variants are considered as one of the main determinants of the concentration of serum lipids and coronary artery disease (CAD). Polymorphisms in the Apolipoprotein (Apo) AI-CIII-AIV gene cluster has been known to affect the concentrations of various lipid sub-fractions and the risk of CAD. The present study assessed associations between polymorphisms of the Apo AI-CIII-AIV gene cluster, [ApoA-I,-75G > A, (rs1799837); ApoC-III 3238C > G, (SstI), (rs5128) and ApoA-IV, Thr347Ser(347A > T), (rs675)] with serum lipids and their contributions to CAD in North Indian population...
December 31, 2016: Cogent Medicine
Na Qiong Wu, Sha Li, Yan Zhang, Cheng Gang Zhu, Yuan Lin Guo, Ying Gao, Ping Qing, Jing Sun, Geng Liu, Qian Dong, Jian Jun Li
OBJECTIVE: Assessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare. METHODS: A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCIII in the association of inflammation with metabolic syndrome (MetS). RESULTS: Patients with MetS showed higher levels of apoCIII [95...
January 2017: Biomedical and Environmental Sciences: BES
Adriene A Paiva, Helena F Raposo, Amarylis C B A Wanschel, Tarlliza R Nardelli, Helena C F Oliveira
Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death...
2017: Oxidative Medicine and Cellular Longevity
Adela Brahimaj, Symen Ligthart, M Arfan Ikram, Albert Hofman, Oscar H Franco, Eric J G Sijbrands, Maryam Kavousi, Abbas Dehghan
OBJECTIVE: We aimed to investigate the role of serum levels of various apolipoproteins on the risk for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We used data from 971 individuals from the prospective population-based Rotterdam Study. We studied the association of HDL cholesterol (HDL-C), apoA1, apoCIII, apoD, and apoE as well as the ratios of apolipoproteins with apoA1 with the risk of T2D. All apolipoproteins, ratios, and HDL-C levels were naturally log-transformed to reach normal distribution...
March 2017: Diabetes Care
Allyson M Morton, Jeremy D Furtado, Jane Lee, William Amerine, Michael H Davidson, Frank M Sacks
BACKGROUND: Lipoprotein subspecies containing apoCIII adversely affect cardiovascular disease (CVD) risk; for example, low density lipoprotein (LDL) with apoCIII is a stronger CVD predictor than LDL without apoCIII. The Epanova for Lowering Very High Triglycerides (EVOLVE) trial showed that Epanova (omega-3 carboxylic acids [OM3-CA]) significantly lowered TG and apoCIII but raised LDL-C. However, it is unknown what subspecies of LDL were affected by treatment. OBJECTIVE: To determine how lipoprotein subspecies are affected by omega-3 fatty acid treatment, we studied the effect of OM3-CA on apoCIII concentrations in high density lipoprotein (HDL), LDL, and very low density lipoprotein (VLDL) and on the concentrations of subspecies of HDL, LDL, and VLDL that contain or do not contain apoCIII...
November 2016: Journal of Clinical Lipidology
Lisa Juntti-Berggren, Per-Olof Berggren
PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing number of patients and a complex, multifactorial pathogenesis. Apolipoprotein (apo) CIII is increased in both types of diabetes and interventions preventing the increase have effects on the development of diabetes. RECENT FINDINGS: ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca-channels. ApoCIII is produced within the pancreatic islets and it increases in parallel with the development of insulin resistance and type-2 diabetes...
February 2017: Current Opinion in Lipidology
Sabine Baumgartner, Ronald P Mensink, Jogchum Plat
BACKGROUND: Evidence is increasing that plant sterols and stanols not only lower fasting serum low-density lipoprotein concentrations, but also those of triglycerides (TG). Insight into effects of these components on postprandial TG metabolism, an emerging risk factor for cardiovascular disease, is missing. OBJECTIVE: Our objective was to examine the 8-hour postprandial response after consuming plant sterol or stanol enriched margarine as part of a mixed meal. METHODS: This postprandial study was part of a randomized crossover study in which 42 subjects consumed plant sterol enriched (3 g/d plant sterols), plant stanol enriched (3 g/d plant stanols), and control margarines for 4 weeks...
2016: PloS One
Yang Li, Zheng Li, Lei Shi, Chenxu Zhao, Bingyu Shen, Ye Tian, Haihua Feng
Atherosclerosis is a chronic inflammatory disease of the vascular walls. ApoCIII is an independent factor which promotes atherosclerotic processes. This study aimed to investigate whether Loganin administration inhibits the inflammatory response in vitro and in vivo. In the apoCIII-induced mouse adipocytes, the levels of cytokines, including TNF-α, MCP-1 and IL-6 were determined by enzyme-linked immunosorbent assay and their gene expressions were measured through RT-PCR. The phosphorylation of nuclear factor-κB (NF-κB) proteins was analyzed by Western blotting...
July 2016: International Immunopharmacology
Yong Chen, Ping Liu, Rong Qi, Yu-Hui Wang, George Liu, Chun Wang
Hypertriglyceridemia (HTG) is a weak risk factor in primary ischemic stroke prevention. However, clinical studies have found a counterintuitive association between a good prognosis after ischemic stroke and HTG. This "HTG paradox" requires confirmation and further explanation. The aim of this study was to experimentally assess this paradox relationship using the gene-modified mice model of extreme HTG. We first used the human Apolipoprotein CIII transgenic (Tg-ApoCIII) mice and non-transgenic (Non-Tg) littermates to examine the effect of HTG on stroke...
May 15, 2016: Brain Research
Andrea Kassai, Ranganath Muniyappa, Amy E Levenson, Mary F Walter, Brent S Abel, Michael Ring, Simeon I Taylor, Sudha B Biddinger, Monica C Skarulis, Phillip Gorden, Rebecca J Brown
Patients with lipodystrophy had elevated apolipoprotein CIII (apoCIII) compared to healthy controls. ApoCIII did not change with leptin treatment despite significant reductions in serum triglyceride.
April 2016: Journal of Clinical Endocrinology and Metabolism
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