التفاصيل البيبلوغرافية
| العنوان: |
USF1 deficiency alleviates inflammation, enhances cholesterol efflux and prevents cholesterol accumulation in macrophages |
| المؤلفون: |
Ruuth, Maija, Soronen, Jarkko, Kaiharju, Essi, Merikanto, Krista, Perttilä, Julia, Metso, Jari, Lee-Rueckert, Miriam, Taskinen, Marja-Riitta, Kovanen, Petri T., Öörni, Katariina, Olkkonen, Vesa M., Jauhiainen, Matti S., Laurila, Pirkka-Pekka |
| المساهمون: |
Medicum, Research Programs Unit, University of Helsinki, Clinicum, Diabetes and Obesity Research Program, Marja-Riitta Taskinen Research Group, Department of Anatomy, Department of Medical and Clinical Genetics, Institute for Molecular Medicine Finland, HUS Internal Medicine and Rehabilitation, HUS Heart and Lung Center |
| بيانات النشر: |
BMC |
| سنة النشر: |
2019 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
USF1, High density lipoproteins, Cholesterol efflux, Cholesterol accumulation, Macrophage, Hepatocyte, Inflammation, FAMILIAL COMBINED HYPERLIPIDEMIA, UPSTREAM TRANSCRIPTION FACTOR-1, HIGH-DENSITY-LIPOPROTEINS, LYSOSOMAL ACID LIPASE, ESTER HYDROLASE 1, FOAM CELLS, HIGH-RISK, ATHEROSCLEROSIS, ASSOCIATION, CAPACITY, 3111 Biomedicine, 1182 Biochemistry, cell and molecular biology |
| الوصف: |
BackgroundThe focus of studies on high-density lipoproteins (HDL) has shifted from HDL-cholesterol (HDL-C) to HDL function. We recently demonstrated that low USF1 expression in mice and humans associates with high plasma HDL-C and low triglyceride levels, as well as protection against obesity, insulin resistance, and atherosclerosis. Here, we studied the impact of USF1 deficiency on HDL functional capacity and macrophage atherogenic functions, including inflammation, cholesterol efflux, and cholesterol accumulation.MethodsWe used a congenic Usf1 deficient mice in C57Bl/6JRccHsd background and blood samples were collected to isolate HDL for structural and functional studies. Lentiviral preparations containing the USF1 silencing shRNA expression vector were used to silence USF1 in human THP-1 and Huh-7 cells. Cholesterol efflux from acetyl-LDL loaded THP-1 macrophages was measured using HDL and plasma as acceptors. Gene expression analysis from USF1 silenced peritoneal macrophages was carried out using Affymetrix protocols.ResultsWe show that Usf1 deficiency not only increases HDL-C levels in vivo, consistent with elevated ABCA1 protein expression in hepatic cell lines, but also improves the functional capacity of HDL particles. HDL particles derived from Usf1 deficient mice remove cholesterol more efficiently from macrophages, attributed to their higher contents of phospholipids. Furthermore, silencing of USF1 in macrophages enhanced the cholesterol efflux capacity of these cells. These findings are consistent with reduced inflammatory burden of USF1 deficient macrophages, manifested by reduced secretion of pro-inflammatory cytokines MCP-1 and IL-1 and protection against inflammation-induced macrophage cholesterol accumulation in a cell-autonomous manner.ConclusionsOur findings identify USF1 as a novel factor regulating HDL functionality, showing that USF1 inactivation boosts cholesterol efflux, reduces macrophage inflammation and attenuates macrophage cholesterol accumulation, linking improved macrophage ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
This study was supported by the Finnish Foundation for Cardiovascular Research (MJ, VMO, PPL, JS), Jenny and Antti Wihuri Foundation (MJ, JS), Novo-Nordisk Foundation (MRT, VMO), Paavo Nurmi Foundation (MJ, PPL, JS, VMO), Academy of Finland (Grant #257545 to MJ and #265940 to KO), Finska Lakaresallskapet (PPL), Aarne Koskelo Foundation (PPL), Emil Aaltonen Foundation (PPL), Foundation for Diabetes Research (PPL, JS), Magnus Ehrnrooth Foundation (PPL, VMO), Jane and Aatos Erkko Foundation (MJ), Sigrid Juselius Foundation (PPL, VMO) and The Finnish Medical Foundation (PPL). Wihuri Research Institute (MR, MLR, KO, PTK) is maintained by the Jenny and Antti Wihuri Foundation.; Ruuth , M , Soronen , J , Kaiharju , E , Merikanto , K , Perttilä , J , Metso , J , Lee-Rueckert , M , Taskinen , M-R , Kovanen , P T , Öörni , K , Olkkonen , V M , Jauhiainen , M S & Laurila , P-P 2018 , ' USF1 deficiency alleviates inflammation, enhances cholesterol efflux and prevents cholesterol accumulation in macrophages ' , Lipids in Health and Disease , vol. 17 , 285 . https://doi.org/10.1186/s12944-018-0930-2Test; ORCID: /0000-0001-8903-0617/work/52400340; ORCID: /0000-0002-6229-3588/work/90756889; 85058544449; de8fd278-34aa-46f9-8fe9-18202e39e9cb; http://hdl.handle.net/10138/287689Test; 000453307200005 |
| الإتاحة: |
http://hdl.handle.net/10138/287689Test |
| حقوق: |
cc_by ; openAccess ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.3F0F31C0 |
| قاعدة البيانات: |
BASE |
