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https://www.readbyqxmd.com/read/28449094/hepatic-tm6sf2-overexpression-affects-cellular-apob-trafficking-plasma-lipid-levels-hepatic-steatosis-and-atherosclerosis
#1
Nicole Ehrhardt, Michael E Doche, Shuang Chen, Hui Z Mao, Meghan T Walsh, Candy Bedoya, Maha Guindi, Weidong Xiong, Joseph Ignatius Irudayam, Jahangir Iqbal, Sebastien Fuchs, Samuel W French, M Mahmood Hussain, Moshe Arditi, Vaithilingaraja Arumugaswami, Miklós Péterfy
The human TM6SF2 gene has been implicated in plasma lipoprotein metabolism, alcoholic and non-alcoholic fatty liver disease and myocardial infarction in multiple genome-wide association studies. To investigate the role of Tm6sf2 in metabolic homeostasis, we generated mice with elevated expression using adeno-associated virus (AAV)-mediated gene delivery. Hepatic overexpression of mouse Tm6sf2 resulted in phenotypes previously observed in Tm6sf2-deficient mice including reduced plasma lipid levels, diminished hepatic TG secretion and increased hepatosteatosis...
April 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28447751/deep-sea-water-improves-hypercholesterolemia-and-hepatic-lipid-accumulation-through-the-regulation-of-hepatic-lipid-metabolic-gene-expression
#2
Kyu-Shik Lee, So-Young Chun, Yun-Suk Kwon, Soyoung Kim, Kyung-Soo Nam
A high‑fat diet or high‑cholesterol diet (HCD) is a major cause of metabolic diseases, including obesity and diabetes; vascular diseases, including hypertension, stroke and arteriosclerosis; and liver diseases, including hepatic steatosis and cirrhosis. The present study aimed to evaluate the effects of deep sea water (DSW) on rats fed a HCD. DSW decreased HCD‑induced increases in total cholesterol and low‑density lipoprotein (LDL) cholesterol in the blood, and recovered high‑density lipoprotein cholesterol...
March 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28446613/structural-basis-for-ligand-capture-and-release-by-the-endocytic-receptor-apoer2
#3
Hidenori Hirai, Norihisa Yasui, Keitaro Yamashita, Sanae Tabata, Masaki Yamamoto, Junichi Takagi, Terukazu Nogi
Apolipoprotein E receptor 2 (ApoER2) is a close homologue of low-density lipoprotein receptor (LDLR) that mediates the endocytosis of ligands, including LDL particles. LDLR family members have been presumed to explore a large conformational space to capture ligands in the extended conformation at the cell surface. Ligands are subsequently released through a pH-titrated structural transition to a self-docked, contracted-closed conformation. In addition to lipoprotein uptake, ApoER2 is implicated in signal transduction during brain development through capture of the extracellular protein reelin...
April 26, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28443021/functional-and-biochemical-endothelial-profiling-in-vivo-in-a-murine-model-of-endothelial-dysfunction-comparison-of-effects-of-1-methylnicotinamide-and-angiotensin-converting-enzyme-inhibitor
#4
Anna Bar, Mariola Olkowicz, Urszula Tyrankiewicz, Edyta Kus, Krzysztof Jasinski, Ryszard T Smolenski, Tomasz Skorka, Stefan Chlopicki
Although it is known that 1-methylnicotinamide (MNA) displays vasoprotective activity in mice, as yet the effect of MNA on endothelial function has not been demonstrated in vivo. Here, using magnetic resonance imaging (MRI) we profile the effects of MNA on endothelial phenotype in mice with atherosclerosis (ApoE/LDLR(-/-)) in vivo, in comparison to angiotensin (Ang) -converting enzyme (ACE) inhibitor (perindopril), with known vasoprotective activity. On a biochemical level, we analyzed whether MNA- or perindopril-induced improvement in endothelial function results in changes in ACE/Ang II-ACE2/Ang-(1-7) balance, and L-arginine/asymmetric dimethylarginine (ADMA) ratio...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28439730/physiological-and-therapeutic-regulation-of-pcsk9-activity-in-cardiovascular-disease
#5
REVIEW
Simon Glerup, Rainer Schulz, Ulrich Laufs, Klaus-Dieter Schlüter
Ischemic heart disease is the main cause of death worldwide and is accelerated by increased levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL-C through its ability to induce degradation of the LDL receptor (LDLR) in the lysosome of hepatocytes. Only in the last few years, a number of breakthroughs in the understanding of PCSK9 biology have been reported illustrating how PCSK9 activity is tightly regulated at several levels by factors influencing its transcription, secretion, or by extracellular inactivation and clearance...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28432645/efficacy-of-lomitapide-in-the-treatment-of-familial-homozygous-hypercholesterolemia-results-of-a-real-world-clinical-experience-in-italy
#6
Laura D'Erasmo, Angelo Baldassare Cefalù, Davide Noto, Antonina Giammanco, Maurizio Averna, Paolo Pintus, Paolo Medde, Giovanni Battista Vigna, Cesare Sirtori, Laura Calabresi, Chiara Pavanello, Marco Bucci, Carlo Sabbà, Patrizia Suppressa, Francesco Natale, Paolo Calabrò, Tiziana Sampietro, Federico Bigazzi, Francesco Sbrana, Katia Bonomo, Fulvio Sileo, Marcello Arca
INTRODUCTION: Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lomitapide in HoFH patients followed with the usual clinical care. METHODS: Clinical and biochemical data were retrospectively collected in 15 HoFH patients (10 with mutations in the LDLR gene and 5 in the LDLRAP1 gene) treated for at least 6 months with lomitapide in addition to lipid-lowering therapies (LLT) in different Lipid Clinics across Italy...
April 21, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#7
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427397/hvc1-ameliorates-hyperlipidemia-and-inflammation-in-ldlr-mice
#8
Se-Yun Cheon, Kyung-Sook Chung, Kyung-Jin Lee, Ho-Young Choi, In-Hye Ham, Dong-Hoon Jung, Yun-Yeop Cha, Hyo-Jin An
BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice fed a high-cholesterol diet for 13 weeks...
April 20, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28424622/pravastatin-chronic-treatment-sensitizes-hypercholesterolemic-mice-muscle-to-mitochondrial-permeability-transition-protection-by-creatine-or-coenzyme-q10
#9
Estela N B Busanello, Ana C Marques, Noelia Lander, Diogo N de Oliveira, Rodrigo R Catharino, Helena C F Oliveira, Anibal E Vercesi
Statins are efficient cholesterol-lowering medicines utilized worldwide. However, 10% of patients suffer from adverse effects specially related to skeletal muscle function. Pro- or anti-oxidant effects of statins have been reported. Here we hypothesized that statins induce muscle mitochondrial oxidative stress leading to mitochondrial permeability transition (MPT) which may explain statin muscle toxicity. Thus, our aims were to investigate the effects of statin chronic treatment on muscle mitochondrial respiration rates, MPT and redox state indicators in the context of hypercholesterolemia...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28422962/docosahexaenoic-acid-blocks-progression-of-western-diet-induced-nonalcoholic-steatohepatitis-in-obese-ldlr-mice
#10
Kelli A Lytle, Carmen P Wong, Donald B Jump
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a major public health concern in western societies. Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, is characterized by hepatic steatosis, inflammation, oxidative stress and fibrosis. NASH is a risk factor for cirrhosis and hepatocellular carcinoma. NASH is predicted to be the leading cause of liver transplants by 2020. Despite this growing public health concern, there remain no Food and Drug Administration (FDA) approved NASH treatments...
2017: PloS One
https://www.readbyqxmd.com/read/28420668/hypercholesterolemia-induces-differentiation-of-regulatory-t-cells-in-the-liver
#11
Reiner K Mailer, Anton Gisterå, Konstantinos A Polyzos, Daniel F Ketelhuth, Göran K Hansson
Rationale: The liver is the central organ that responds to dietary cholesterol intake and facilitates the release and clearance of lipoprotein particles. Persistent hypercholesterolemia leads to immune responses against lipoprotein particles that drive atherosclerosis. However, the effect of hypercholesterolemia on hepatic T cell differentiation remains unknown. Objective: To investigate hepatic T cell subsets upon hypercholesterolemia. Methods and Results: We observed that hypercholesterolemia elevated the intrahepatic regulatory T (Treg) cell population and increased the expression of transforming growth factor beta 1 in the liver...
April 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28410578/serum-low-density-lipoprotein-and-low-density-lipoprotein-expression-level-at-diagnosis-are-favorable-prognostic-factors-in-patients-with-small-cell-lung-cancer-sclc
#12
Ting Zhou, Jianhua Zhan, Wenfeng Fang, Yuanyuan Zhao, Yunpeng Yang, Xue Hou, Zhonghan Zhang, Xiaobo He, Yaxiong Zhang, Yan Huang, Li Zhang
BACKGROUND: Patients with small-cell lung cancer (SCLC) patients demonstrate varied survival outcomes. Previous studies have reported that lipoproteins are associated with prognosis in various cancers; however, the role of low-density lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients with SCLC has not been studied. METHODS: In this study, the impact of LDL and LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients with SCLC were retrospectively evaluated, in which 198 patients had adequate tissues for immunohistochemistry, and serum LDL and LDLR expression levels at baseline were tested...
April 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28405938/genetic-architecture-of-familial-hypercholesterolaemia
#13
REVIEW
Mahtab Sharifi, Marta Futema, Devaki Nair, Steve E Humphries
PURPOSE OF REVIEW: Familial hypercholesterolaemia (FH) is an inherited disorder of low-density lipoprotein cholesterol (LDL-C) which is characterised by a raised cholesterol level from birth and a high risk of premature coronary heart disease. In this paper, we review the genetic basis of FH and its impact on the clinical presentation. RECENT FINDINGS: Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH...
May 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28404852/attachment-and-post-attachment-receptors-important-for-hepatitis-c-virus-infection-and-cell-to-cell-transmission
#14
Huahao Fan, Luhua Qiao, Kyung-Don Kang, Junfen Fan, Wensheng Wei, Guangxiang Luo
Hepatitis C virus (HCV) infection requires multiple receptors for its attachment and entry to the cell. Our previous studies found that human syndecan-1 (SDC-1), SDC-2, and T cell immunoglobulin and mucin domain-containing protein 1 (TIM-1) are HCV attachment receptors. Other cell surface molecules such as CD81, CLDN1, OCLN, SR-BI, and LDLR mainly function at post-attachment steps, which are considered post-attachment receptors. The underlying molecular mechanisms of different receptors in HCV cell-free and cell-to-cell transmission remain elusive...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28399420/dietary-rose-hip-exerts-antiatherosclerotic-effects-and-increases-nitric-oxide-mediated-dilation-in-apoe-null-mice
#15
Michele Cavalera, Ulrika Axling, Catarina Rippe, Karl Swärd, Cecilia Holm
Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans...
March 21, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28391914/the-montreal-fh-score-a-new-score-to-predict-cardiovascular-events-in-familial-hypercholesterolemia
#16
Martine Paquette, Robert Dufour, Alexis Baass
BACKGROUND: Familial hypercholesterolemia (FH) is characterized by extremely high low-density lipoprotein cholesterol (LDL-C) concentration and premature cardiovascular disease (CVD). Not all FH patients present the same CVD risk, and currently, there is no clinical tool to assess this risk. OBJECTIVE: The objectives of this cross-sectional cohort study are twofold: to identify the strongest predictors of CVD in patients with FH and to develop a new score to identify FH patients at very high CVD risk...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28391882/clinical-and-molecular-aspects-of-familial-hypercholesterolemia-in-ibero-american-countries
#17
Raul D Santos, Mafalda Bourbon, Rodrigo Alonso, Ada Cuevas, Norma Alexandra Vasques-Cardenas, Alexandre C Pereira, Alonso Merchan, Ana Catarina Alves, Ana Margarida Medeiros, Cinthia E Jannes, Jose E Krieger, Laura Schreier, Leopoldo Perez de Isla, Maria Teresa Magaña-Torres, Mario Stoll, Nelva Mata, Nicolas Dell Oca, Pablo Corral, Sylvia Asenjo, Virginia G Bañares, Ximena Reyes, Pedro Mata
BACKGROUND: There is little information about familial hypercholesterolemia (FH) epidemiology and care in Ibero-American countries. The Ibero-American FH network aims at reducing the gap on diagnosis and treatment of this disease in the region. OBJECTIVE: To describe clinical, molecular, and organizational characteristics of FH diagnosis in Argentina, Brazil, Chile, Colombia, Mexico, Portugal, Spain, and Uruguay. METHODS: Descriptive analysis of country data related to FH cascade screening, molecular diagnosis, clinical practice guidelines, and patient organization presence in Ibero-America...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28387708/the-effect-of-low-dose-proteasome-inhibition-on-pre-existing-atherosclerosis-in-ldl-receptor-deficient-mice
#18
Nicola Wilck, Mandy Fechner, Cristian Dan, Verena Stangl, Karl Stangl, Antje Ludwig
Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in atherosclerosis development. However, the nature of UPS dysfunction has been proposed to be specific to certain stages of atherosclerosis development, which has implications for proteasome inhibition as a potential treatment option. Recently, low-dose proteasome inhibition with bortezomib has been shown to attenuate early atherosclerosis in low-density lipoprotein receptor-deficient (LDLR(-/-)) mice. The present study investigates the effect of low-dose proteasome inhibition with bortezomib on pre-existing advanced atherosclerosis in LDLR(-/-) mice...
April 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28381441/role-of-lrp1-in-the-pathogenesis-of-alzheimer-s-disease-evidence-from-clinical-and-preclinical-studies
#19
Mitsuru Shinohara, Masaya Tachibana, Takahisa Kanekiyo, Guojun Bu
Among the low-density lipoprotein receptor (LDLR) family members, the roles of LDLR-related protein 1 (LRP1 or LRP) in the pathogenesis of Alzheimer's disease (AD), especially late-onset AD, have been the most studied by genetic, neuropathological and biomarker analyses (clinical studies) or cellular and animal model systems (preclinical studies) over the last 25 years. Although there are some conflicting reports, accumulating evidence from preclinical studies indicates that LRP1 not only regulates the metabolism of amyloid-β peptides (Aβ) in the brain and periphery, but also maintains brain homeostasis, impairment of which likely contributes to AD development in Aβ-independent manners...
April 4, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28379029/molecular-genetic-background-of-an-autosomal-dominant-hypercholesterolemia-in-the-czech-republic
#20
L Tichý, L Fajkusová, P Zapletalová, L Schwarzová, M Vrablík, T Freiberger
Autosomal dominant hypercholesterolemia (ADH), more known as familial hypercholesterolemia (FH), is a lipid metabolism disorder characterized by an elevation in low-density lipoprotein cholesterol (LDL-C) and increased risk for cardiovascular disease. In this study, we assessed a spectrum of mutations causing ADH in 3914 unrelated Czech patients with clinical diagnosis of hypercholesterolemia. Samples have been collected within the framework of the MedPed project running in the Czech Republic since 1998. So far we have found 432 patients (11...
April 5, 2017: Physiological Research
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