keyword
https://read.qxmd.com/read/38490635/a-targeted-proteomics-method-for-quantifying-plasma-apolipoprotein-kinetics-in-individual-mice-using-stable-isotope-labeling
#1
JOURNAL ARTICLE
Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt
Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be collected at sequential time points from individual mice. We describe a targeted liquid chromatography tandem mass spectrometry method for simultaneously quantifying the stable isotope enrichment of several apolipoproteins represented by multiple peptides in serial blood samples (15 μL each) obtained after retro-orbital injection of 13 C6 ,15 N2 -lysine (Lys8) in mice...
March 13, 2024: Journal of Lipid Research
https://read.qxmd.com/read/38473885/a-mass-spectrometry-based-proteome-study-of-twin-pairs-discordant-for-incident-acute-myocardial-infarction-within-three-years-after-blood-sampling-suggests-novel-biomarkers
#2
JOURNAL ARTICLE
Hans Christian Beck, Asmus Cosmos Skovgaard, Afsaneh Mohammadnejad, Nicolai Bjødstrup Palstrøm, Palle Fruekilde Nielsen, Jonas Mengel-From, Jacob Hjelmborg, Lars Melholt Rasmussen, Mette Soerensen
Acute myocardial infarction (AMI) is a major cause of mortality and morbidity worldwide, yet biomarkers for AMI in the short- or medium-term are lacking. We apply the discordant twin pair design, reducing genetic and environmental confounding, by linking nationwide registry data on AMI diagnoses to a survey of 12,349 twins, thereby identifying 39 twin pairs (48-79 years) discordant for their first-ever AMI within three years after blood sampling. Mass spectrometry of blood plasma identified 715 proteins. Among 363 proteins with a call rate > 50%, imputation and stratified Cox regression analysis revealed seven significant proteins (FDR < 0...
February 24, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38464296/epigenetic-programming-of-host-lipid-metabolism-associates-with-resistance-to-tst-igra-conversion-after-exposure-to-mycobacterium-tuberculosis
#3
Kimberly A Dill-McFarland, Jason D Simmons, Glenna J Peterson, Felicia K Nguyen, Monica Campo, Penelope Benchek, Catherine M Stein, Tomas Vaisar, Harriet Mayanja-Kizza, W Henry Boom, Thomas R Hawn
UNLABELLED: Mycobacterium tuberculosis (Mtb) exposure leads to a range of outcomes including clearance, latent TB infection (LTBI), and pulmonary tuberculosis (TB). Some heavily exposed individuals resist tuberculin skin test (TST) and interferon gamma release assay (IGRA) conversion (RSTR), which suggests that they employ IFNγ-independent mechanisms of Mtb control. Here, we compare monocyte epigenetic profiles of RSTR and LTBI from a Ugandan household contact cohort. Chromatin accessibility did not differ between uninfected RSTR and LTBI monocytes...
March 4, 2024: bioRxiv
https://read.qxmd.com/read/38459255/a-novel-mouse-model-of-familial-combined-hyperlipidemia-and-atherosclerosis
#4
JOURNAL ARTICLE
Mei-Jie Chen, Yi-Tong Xu, Lu Sun, Zhi-Hua Wang, Peter J Little, Li Wang, Xun-de Xian, Jian-Ping Weng, Suo-Wen Xu
Within the context of residual cardiovascular risk in post-statin era, emerging evidence from epidemiologic and human genetic studies have demonstrated that triglyceride (TG)-rich lipoproteins and their remnants are causally related to cardiovascular risk. While, carriers of loss-of-function mutations of ApoC3 have low TG levels and are protected from cardiovascular disease (CVD). Of translational significance, siRNAs/antisense oligonucleotide (ASO) targeting ApoC3 is beneficial for patients with atherosclerotic CVD...
March 8, 2024: Acta Pharmacologica Sinica
https://read.qxmd.com/read/38454133/weighted-burden-analysis-of-rare-coding-variants-in-470-000-exome-sequenced-uk-biobank-participants-characterises-effects-on-hyperlipidaemia-risk
#5
JOURNAL ARTICLE
David Curtis
A previous study of 200,000 exome-sequenced UK Biobank participants investigating the association between rare coding variants and hyperlipidaemia had implicated four genes, LDLR, PCSK9, APOC3 and IFITM5, at exome-wide significance. In addition, a further 43 protein-coding genes were significant with an uncorrected p value of <0.001. Exome sequence data has become available for a further 270,000 participants and weighted burden analysis to test for association with hyperlipidaemia was carried out in this sample for the 47 genes highlighted by the previous study...
March 7, 2024: Journal of Human Genetics
https://read.qxmd.com/read/38441531/foxo6-mediated-apoc3-upregulation-promotes-hepatic-steatosis-and-hyperlipidemia-in-aged-rats-fed-a-high-fat-diet
#6
JOURNAL ARTICLE
Dae Hyun Kim, Seulah Lee, Sang Gyun Noh, Jaewon Lee, Hae Young Chung
FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation. In order to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts, we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO)...
March 3, 2024: Aging
https://read.qxmd.com/read/38418429/parvb-and-hsd17b13-variants-are-associated-with-nonalcoholic-fatty-liver-disease-in-children
#7
JOURNAL ARTICLE
Kyung Jae Lee, Jin Soo Moon, Jin Gyu Lim, Homin Huh, Jeong Eun Ahn, Lia Kim, Nan Young Kim, Jae Sung Ko
BACKGROUND AND AIM: The aim of this study was to investigate the comprehensive genetic effects of exploratory variants of LYPLAL1, GCKR, HSD17B13, TRIB1, APOC3, MBOAT7, and PARVB on pediatric nonalcoholic fatty liver disease in addition to the previously reported variants of TM6SF2, PNPLA3, and SAMM50 in Korean children. METHODS: A prospective case-control study was conducted involving 309 patients diagnosed using ultrasound and 339 controls. Anthropometric measurements, liver function tests, and metabolic marker analysis were conducted, and fibrosis scores were calculated...
February 28, 2024: Journal of Gastroenterology and Hepatology
https://read.qxmd.com/read/38416767/potential-association-of-genetically-predicted-lipid-and-lipid-modifying-drugs-with-rheumatoid-arthritis-a-mendelian-randomization-study
#8
JOURNAL ARTICLE
Zhican Huang, Ting Cui, Jin Yao, Yutong Wu, Jun Zhu, Xin Yang, Li Cui, Haiyan Zhou
BACKGROUND: Past studies have demonstrated that patients diagnosed with rheumatoid arthritis (RA) often exhibit abnormal levels of lipids. Furthermore, certain lipid-modifying medications have shown effectiveness in alleviating clinical symptoms associated with RA. However, the current understanding of the causal relationship between lipids, lipid-modifying medications, and the risk of developing RA remains inconclusive. This study employed Mendelian randomization (MR) to investigate the causal connection between lipids, lipid-modifying drugs, and the occurrence of RA...
2024: PloS One
https://read.qxmd.com/read/38390206/genetic-association-of-lipid-lowering-drug-target-genes-with-erectile-dysfunction-and-male-reproductive-health
#9
JOURNAL ARTICLE
Quanxin Su, Rui Wang, Yayin Luo, Qizhen Tang, Kenan Wang
OBJECTIVE: The effect of hypolipidemic drugs on male erectile function is still controversial. This Mendelian randomization (MR) study aimed to explore the potential impact of lipid-lowering drug targets on ED. METHODS: We collected seven genetic variants encoding lipid-lowering drug targets (LDLR, HMGCR, NPC1L1, PCSK9, APOB, APOC3 and LPL) from published genome-wide association study (GWAS) statistics, and performed drug target MR analysis. The risk of ED was defined as the primary outcome, sex hormone levels and other diseases as the secondary outcomes...
2024: Frontiers in Endocrinology
https://read.qxmd.com/read/38345009/apolipoprotein-c-iii-amyloidosis-in-white-lions-panthera-leo
#10
JOURNAL ARTICLE
Natsumi Kobayashi, Susumu Iwaide, Hiroto Fukui, Yumi Une, Yoshiyuki Itoh, Miki Hisada, Tomoaki Murakami
Apolipoprotein C-III (ApoC-III) amyloidosis in humans is a hereditary amyloidosis caused by a D25V mutation in the APOC3 gene. This condition has only been reported in a French family and not in animals. We analyzed a 19-year-old white lion ( Panthera leo ) that died in a Japanese safari park and found renal amyloidosis characterized by severe deposition confined to the renal corticomedullary border zone. Mass spectrometry-based proteomic analysis identified ApoC-III as a major component of renal amyloid deposits...
February 12, 2024: Veterinary Pathology
https://read.qxmd.com/read/38336686/rare-and-common-coding-variants-in-lipid-metabolism-related-genes-and-their-association-with-coronary-artery-disease
#11
JOURNAL ARTICLE
Wei Li, Yongyi Wang, Ritai Huang, Feng Lian, Genxing Xu, Weijun Wang, Song Xue
BACKGROUND: Coronary artery disease (CAD) is a complex disease that is influenced by environmental and genetic factors. In this study, we aimed to investigate the relationship between coding variants in lipid metabolism-related genes and CAD in a Chinese Han population. METHODS: A total of 252 individuals were recruited for this study, including 120 CAD patients and 132 healthy control individuals. Rare and common coding variants in 12 lipid metabolism-related genes (ANGPTL3, ANGPTL4, APOA1, APOA5, APOC1, APOC3, CETP, LDLR, LIPC, LPL, PCSK9 and SCARB1) were detected via next-generation sequencing (NGS)-based targeted sequencing...
February 9, 2024: BMC Cardiovascular Disorders
https://read.qxmd.com/read/38334488/apoc3-sirna-and-aso-therapy-for-dyslipidemia
#12
JOURNAL ARTICLE
Jasmine Chebli, Miriam Larouche, Daniel Gaudet
PURPOSE OF REVIEW: The aim of this review is to present the clinical indications of apolipoprotein C-III (apoC3) inhibition in the therapeutic arsenal for the treatment of lipid disorders and associated risks and to compare the most advanced modalities of apoC3 inhibition currently available or in development, specifically APOC3 antisense oligonucleotides (ASO) and small interfering RNA (siRNA). RECENT FINDINGS: ApoC3 inhibition significantly decreases triglyceride levels by mechanisms coupling both lipoprotein lipase (LPL) upregulation and LPL-independent mechanisms...
February 12, 2024: Current Opinion in Endocrinology, Diabetes, and Obesity
https://read.qxmd.com/read/38320508/randomized-phase-i-trials-one-size-fits-all
#13
EDITORIAL
Susan Halabi, Codruta Chiuzan
In this issue of NEJM Evidence , Gaudet et al. present the safety profile and pharmacodynamics of ARO-APOC3, a small interfering RNA therapeutic that inhibits apolipoprotein C-III (APOC3) mRNA expression in a phase I trial.1 Assignment to treatment was based on fasting levels of triglycerides. The trial included two double-blinded cohorts with 52 randomly assigned healthy participants and 40 patients with hypertriglyceridemia assigned to escalating doses of ARO-APOC3 at 10, 25, 50, or 100 mg or placebo in a single- and/or repeat-dose (days 1 and 29) regimen...
December 2023: NEJM Evid
https://read.qxmd.com/read/38320505/apolipoprotein-c-iii-inhibition-killing-two-birds-with-one-stone
#14
EDITORIAL
Jordan M Kraaijenhof, Erik S G Stroes
In this issue of NEJM Evidence , Gaudet et al.1 report on safety and efficacy of a strategy targeting apolipoprotein C-III (APOC3) using a silencing ribonucleic acid (RNA; ARO-APOC3). In a phase I trial comprising 52 healthy volunteers (triglycerides [TG], >80 mg/dl), 40 patients with hypertriglyceridemia (TG, >300 mg/dl), and 20 patients with chylomicronemia (TG, >880 mg/dl), ARO-APOC3 or placebo was administered subcutaneously either once or twice, with doses given on days 1 and 29...
December 2023: NEJM Evid
https://read.qxmd.com/read/38320498/rna-interference-therapy-targeting-apolipoprotein-c-iii-in-hypertriglyceridemia
#15
JOURNAL ARTICLE
Daniel Gaudet, Peter Clifton, David Sullivan, John Baker, Christian Schwabe, Susan Thackwray, Russell Scott, James Hamilton, Bruce Given, Stacey Melquist, Rong Zhou, Ting Chang, Javier San Martin, Gerald F Watts, Ira J Goldberg, Joshua W Knowles, Robert A Hegele, Christie M Ballantyne
APOC3-Targeting RNAi for HypertriglyceridemiaThis randomized controlled trial examined the safety and side effects of the small interfering RNA ARO-APOC3 in healthy volunteers and patients with hypertriglyceridemia and chylomicronemia. ARO-APOC3 was associated with few adverse events and no dose-limiting toxicities.
December 2023: NEJM Evid
https://read.qxmd.com/read/38317742/genetic-and-epigenetic-determinants-of-non-alcoholic-fatty-liver-disease-nafld-in-lean-individuals-a-systematic-review
#16
REVIEW
Basile Njei, Yazan A Al-Ajlouni, Derek Ugwendum, Manasik Abdu, Anim Forjindam, Mouhand F Mohamed
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common in obese individuals, but its occurrence in lean individuals and the underlying mechanisms are not well understood. This study aimed to systematically review the literature on the genetic and epigenetic factors influencing NAFLD in lean individuals. METHODS: A comprehensive search was conducted on April 2nd , 2023, in seven databases using specific criteria. Only peer-reviewed studies in English, focusing on genetic or epigenetic effects on NAFLD in lean individuals, were included for qualitative synthesis...
2024: Translational Gastroenterology and Hepatology
https://read.qxmd.com/read/38299167/advances-in-dyslipidaemia-treatments-focusing-on-apoc3-and-angptl3-inhibitors
#17
REVIEW
Brian Tomlinson, Qian-Yan Wu, Yi-Ming Zhong, Yan-Hong Li
Apolipoprotein C3 (apoC3) and angiopoietin-like protein 3 (ANGPTL3) inhibit lipolysis by lipoprotein lipase and may influence the secretion and uptake of various lipoproteins. Genetic studies show that depletion of these proteins is associated with improved lipid profiles and reduced cardiovascular events so it was anticipated that drugs which mimic the effects of loss-of-function mutations would be useful lipid treatments. ANGPTL3 inhibitors were initially developed as a treatment for severe hypertriglyceridaemia including familial chylomicronaemia syndrome (FCS), which is usually not adequately controlled with currently available drugs...
January 2024: Journal of lipid and atherosclerosis
https://read.qxmd.com/read/38287401/correlations-between-genetically-predicted-lipid-lowering-drug-targets-and-inflammatory-bowel-disease
#18
JOURNAL ARTICLE
Kuiyuan Huang, Shenan Huang, Ming Xiong
BACKGROUND: Millions of individuals globally suffer from Inflammatory bowel diseases (IBDs). There is a dearth of large population-based investigations on lipid metabolism and IBDs, and it is unclear whether lipid-lowering drugs target IBDs causally. Consequently, the aim of this study was to investigate the effects of lipid-lowering medication targets on the occurrence and progression of IBDs. METHODS: Among the more than 400,000 participants in the UK Biobank cohort and the more than 170,000 participants in the Global Lipids Genetics Consortium, a total of nine genes linked to lipid-lowering drug targets were obtained (ABCG5/ABCG8, APOB, APOC3, LDLR, LPL, HMGCR, NPC1L1, PCSK9, and PPARA)...
January 29, 2024: Lipids in Health and Disease
https://read.qxmd.com/read/38275377/unlocking-the-medicinal-mysteries-preventing-lacunar-stroke-with-drug-repurposing
#19
JOURNAL ARTICLE
Linjing Zhang, Fan Wang, Kailin Xia, Zhou Yu, Yu Fu, Tao Huang, Dongsheng Fan
Currently, only the general control of the risk factors is known to prevent lacunar cerebral infarction, but it is unknown which type of medication for controlling the risk factors has a causal relationship with reducing the risk of lacunar infarction. To unlock this medical mystery, drug-target Mendelian randomization analysis was applied to estimate the effect of common antihypertensive agents, hypolipidemic agents, and hypoglycemic agents on lacunar stroke. Lacunar stroke data for the transethnic analysis were derived from meta-analyses comprising 7338 cases and 254,798 controls...
December 20, 2023: Biomedicines
https://read.qxmd.com/read/38232538/apolipoprotein-c3-apoc3-facilitates-nlrp3-mediated-pyroptosis-of-macrophages-through-mitochondrial-damage-by-accelerating-of-the-interaction-between-scimp-and-syk-pathway-in-acute-lung-injury
#20
JOURNAL ARTICLE
Zhichen Pu, Wenhui Wang, Haitang Xie, Wusan Wang
Respiratory failure caused by severe acute lung injury (ALI) is the main cause of mortality in patients with COVID-19.This study aimed to investigate the effects and underlying biological mechanism of Apolipoprotein C3 (ApoC3) in ALI. To establish an in vivo model, C57BL/6 mice were exposed by lipopolysaccharide (LPS). For the in vitro model, murine bone marrow-derived macrophages (BMDMs) or RAW264.7 cells were stimulated with LPS + adenosine triphosphate (ATP). Serum levels of ApoC3 were found to be upregulated in patients with COVID-19 or pneumonia-induced ALI...
January 16, 2024: International Immunopharmacology
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