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https://www.readbyqxmd.com/read/29047330/deletion-of-the-nr4a-nuclear-receptor-nor1-in-hematopoietic-stem-cells-reduces-inflammation-but-not-abdominal-aortic-aneurysm-formation
#1
Hua Qing, Karrie L Jones, Elizabeth B Heywood, Hong Lu, Alan Daugherty, Dennis Bruemmer
BACKGROUND: The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a constitutively active transcription factor to regulate inflammation, proliferation, and cell survival during pathological vascular remodeling. Inflammatory processes represent key mechanisms leading to abdominal aortic aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been investigated previously. METHODS: Inflammatory gene expression was analyzed in bone marrow-derived macrophages isolated from NOR1-deficient mice...
October 18, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/29046274/genetic-depletion-or-hyperresponsiveness-of-natural-killer-cells-do-not-affect-atherosclerosis-development
#2
Wared Nour Eldine, Jeremie Joffre, Kazem Zibara, Andreas Giraud, Bruno Esposito, Lynda Zeboudj, José Vilar, Megumi Terada, Patrick Bruneval, Eric Vivier, Hafid Ait-Oufella, Ziad Mallat, Sophie Ugolini, Alain Tedgui
Rationale: Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunity are involved. Although several studies have evaluated the functions of NK cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or pro-atherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss- or gain-of-function of NK cells. Objective: We used two selective genetic approaches to investigate the role of NK cells in atherosclerosis: 1) Ncr1i(Cre/+)R26(lsl-DTA/+) mice in which NK cells were depleted, 2) Noé mice in which NK cells are hyperresponsive...
October 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/29042581/immunoproteasome-subunit-%C3%A3-5i-lmp7-deficiency-in-atherosclerosis
#3
Bernd Hewing, Antje Ludwig, Cristian Dan, Max Pötzsch, Carmen Hannemann, Andreas Petry, Dilyara Lauer, Agnes Görlach, Elena Kaschina, Dominik N Müller, Gert Baumann, Verena Stangl, Karl Stangl, Nicola Wilck
Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR(-/-)LMP7(-/-) and LDLR(-/-) mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038147/imputation-of-baseline-ldl-cholesterol-concentration-in-patients-with-familial-hypercholesterolemia-on-statins-or-ezetimibe
#4
Isabelle Ruel, Sumayah Aljenedil, Iman Sadri, Émilie de Varennes, Robert A Hegele, Patrick Couture, Jean Bergeron, Eric Wanneh, Alexis Baass, Robert Dufour, Daniel Gaudet, Diane Brisson, Liam R Brunham, Gordon A Francis, Lubomira Cermakova, James M Brophy, Arnold Ryomoto, G B John Mancini, Jacques Genest
BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy...
October 16, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29036927/chinese-olive-canarium-album-l-fruit-extract-attenuates-metabolic-dysfunction-in-diabetic-rats
#5
Yu-Te Yeh, An-Na Chiang, Shu-Chen Hsieh
Hyperglycemia and dysregulation of lipid metabolism play a crucial role in metabolic dysfunction. The aims of present study were to evaluate the ameliorative effect of the ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc) on high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic rats. CO-EtOAc, rich in gallic acid and ellagic acid, could markedly decreased the body weight and epididymal adipose mass. In addition, CO-EtOAc increased serum HDL-C levels, hepatic GSH levels, and antioxidant enzyme activities; lowered blood glucose, serum levels of total cholesterol (TC), triglycerides (TG), bile acid, and tumor necrosis factor alpha (TNFα); and reduced TC and TG in liver...
October 15, 2017: Nutrients
https://www.readbyqxmd.com/read/29035781/lack-of-myeloid-fatp1-increases-atherosclerotic-lesion-size-in-ldlr-mice
#6
Liyang Zhao, Alyssa J Cozzo, Amy R Johnson, Taylor Christensen, Alex J Freemerman, James E Bear, Jeremy D Rotty, Brian J Bennett, Liza Makowski
BACKGROUND AND AIMS: Altered metabolism is an important regulator of macrophage (MΦ) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated MΦs (CAM) are glycolytic while alternatively-activated MΦs (AAM) oxidize fatty acids, although overlap exists. We previously demonstrated that MΦ fatty acid transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity...
October 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29030613/lipopolysaccharide-enters-the-rat-brain-by-a-lipoprotein-mediated-transport-mechanism-in-physiological-conditions
#7
Alejandra Vargas-Caraveo, Aline Sayd, Sandra R Maus, Javier R Caso, José L M Madrigal, Borja García-Bueno, Juan C Leza
Physiologically, lipopolysaccharide (LPS) is present in the bloodstream and can be bound to several proteins for its transport (i.e.) LPS binding protein (LBP) and plasma lipoproteins). LPS receptors CD14 and TLR-4 are constitutively expressed in the Central Nervous System (CNS). To our knowledge, LPS infiltration in CNS has not been clearly demonstrated. A naturalistic experiment with healthy rats was performed to investigate whether LPS is present with its receptors in brain. Immunofluorescences showed that lipid A and core LPS were present in circumventricular organs, choroid plexus, meningeal cells, astrocytes, tanycytes and endothelial cells...
October 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030487/macrophage-specific-expression-of-il-37-in-hyperlipidemic-mice-attenuates-atherosclerosis
#8
Sara McCurdy, Yvonne Baumer, Emma Toulmin, Bog-Hieu Lee, William A Boisvert
Atherosclerosis, the progressive buildup of plaque within arterial blood vessels, can lead to fatal downstream events, such as heart attack or stroke. A key event contributing to the development of atherosclerosis is the infiltration of monocytes and its associated inflammation, as well as the formation of lipid-laden macrophage foam cells within the vessel wall. IL-37 is recognized as an important anti-inflammatory cytokine expressed especially by immune cells. This study was undertaken to elucidate the role of macrophage-expressed IL-37 in reducing the production and effects of proinflammatory cytokines, preventing foam cell formation, and reducing the development of atherosclerosis...
October 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29029037/functional-variants-in-the-low-density-lipoprotein-receptor-gene-are-associated-with-clear-cell-renal-cell-carcinoma-susceptibility
#9
Gui-Ming Zhang, Meng-Yun Wang, Ya-Nan Liu, Yao Zhu, Fang-Ning Wan, Qing-Yi Wei, Ding-Wei Ye
Recent studies indicate that abnormal levels of low-density lipoprotein (LDL), which is an important component of dyslipidaemia, are associated with alterations to cancer risk, including that of renal cell carcinoma (RCC). Single nucleotide polymorphisms at microRNA-binding sites contribute to cancer susceptibility and progression by affecting the mRNA function of target genes. In this case-control study, we examined the frequency of six potentially functional single nucleotide polymorphisms in the LDL receptor gene (LDLR) in 1004 clear cell RCC (ccRCC) patients and 1065 cancer-free subjects...
September 22, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29024862/4-phenylbutyrate-and-valproate-treatment-attenuates-the-progression-of-atherosclerosis-and-stabilizes-existing-plaques
#10
Aric Huang, Tayler L Young, Vi T Dang, Yuanyuan Shi, Cameron S McAlpine, Geoff H Werstuck
BACKGROUND AND AIMS: Recent evidence suggests that endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)-3α/β is involved in the activation of pro-atherosclerotic processes. In this study, we examined the effects of small molecules that interfere with ER stress-GSK3α/β signaling on the progression and regression of atherosclerosis in a mouse model. METHODS: To examine atherosclerotic progression, low-density lipoprotein receptor deficient (Ldlr(-/-)) mice were placed on a high-fat diet (HFD) and treated with the chemical chaperone, 4-phenylbutyrate (4PBA, 3...
September 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29021777/circulating-cholesterol-levels-may-link-to-the-factors-influencing-parkinson-s-risk
#11
Lijun Zhang, Xue Wang, Ming Wang, Nick W Sterling, Guangwei Du, Mechelle M Lewis, Tao Yao, Richard B Mailman, Runze Li, Xuemei Huang
OBJECTIVES: A growing literature suggests that circulating cholesterol levels have been associated with Parkinson's disease (PD). In this study, we investigated a possible causal basis for the cholesterol-PD link. METHODS: Fasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1) were chosen as confounding variables because they may influence both cholesterol levels and PD risk...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29016728/augmented-th17-differentiation-in-trim21-deficiency-promotes-a-stable-phenotype-of-atherosclerotic-plaques-with-high-collagen-content
#12
Susanna Brauner, Xintong Jiang, Gudny Ella Thorlacius, Anna M Lundberg, Therese Östberg, Zhong-Qun Yan, Vijay K Kuchroo, Göran K Hansson, Marie Wahren-Herlenius
Aims: Patients with hyperlipidemia are at risk of atherosclerosis, but not all develop cardiovascular disease, highlighting the importance of other risk factors such as inflammation. Both the innate and adaptive arms of the immune system have been suggested in the initiation and propagation of plaque formation. Tri-partite motif (TRIM) 21 is a regulator of tissue inflammation and pro-inflammatory cytokine production, and has been implicated in chronic inflammatory disease. Here, we investigate a potential role for TRIM21 in coronary artery disease...
September 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28993407/heterozygous-null-ldlr-mutation-in-a-familial-hypercholesterolemia-patient-with-an-atypical-presentation-because-of-alcohol-abuse
#13
Kamaldeep Panach, Abhimanyu Garg, Zahid Ahmad
No abstract text is available yet for this article.
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28990215/ultrasonic-perfluorohexane-loaded-monocyte-imaging-toward-a-minimally-invasive-technique-for-selective-detection-of-liver-inflammation-in-fatty-liver-disease
#14
Koen D Reesink, Tim Hendrikx, Patrick J van Gorp, Arnold P Hoeks, Ronit Shiri-Sverdlov
OBJECTIVES: To investigate the utility of ultrasonic (US) perfluorohexane (PFH)-loaded monocyte imaging for detection of liver inflammation in fatty liver disease. METHODS: C57Bl6 mice were injected intraperitoneally with tumor necrosis factor α and assessed by US PFH-loaded monocyte imaging 3 hours later. Echogenic monocytes were injected intravenously, leading to a transient increase in liver tissue intensity on a US perfusion scan. The contrast wash-out time constant was hypothesized to reflect the degree of inflammation...
October 9, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28987238/thyroid-stimulating-hormone-exhibits-the-impact-on-ldlr-ldl-c-via-up-regulating-hepatic-pcsk9-expression
#15
Yingyun Gong, Yizhe Ma, Zhengqin Ye, Zhenzhen Fu, Panpan Yang, Beibei Gao, Wen Guo, Dandan Hu, Jingya Ye, Shuai Ma, Fan Zhang, Li Zhou, Xinyu Xu, Zhong Li, Tao Yang, Hongwen Zhou
CONTEXT: Thyroid stimulating hormone (TSH) has received increasing attention as being closely associated with increased low-density lipoprotein cholesterol (LDL-c) level and higher atherosclerotic risks. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is known for increasing circulating LDL-c level by inducing LDL receptor degradation. However, whether TSH influences hepatic PCSK9 expression and LDL-c metabolism remains unclear. METHODS: First, the correlation between TSH and lipid profiles were investigated in euthyroid population and in subclinical hypothyroidism patients...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28984832/the-role-of-omega-3-fatty-acids-in-reverse-cholesterol-transport-a-review
#16
REVIEW
Alex Pizzini, Lukas Lunger, Egon Demetz, Richard Hilbe, Guenter Weiss, Christoph Ebenbichler, Ivan Tancevski
The beneficial effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on cardiovascular disease have been studied extensively. However, it remains unclear to what extent n-3 PUFAs may impact Reverse Cholesterol Transport (RCT). RCT describes a mechanism by which excess cholesterol from peripheral tissues is transported to the liver for hepatobiliary excretion, thereby inhibiting foam cell formation and the development of atherosclerosis. The aim of this review is to summarize the literature and to provide an updated overview of the effects of n-3 PUFAs on key players in RCT, including apoliprotein AI (apoA-I), ATP-binding cassette transporter A1 (ABCA1), ABCG1, apoE, scavenger receptor class B type I (SR-BI), cholesteryl ester transfer protein (CETP), low-density lipoprotein receptor (LDLr), cholesterol 7 alpha-hydroxylase (CYP7A1) and ABCG5/G8...
October 6, 2017: Nutrients
https://www.readbyqxmd.com/read/28983592/amygdalin-ameliorates-the-progression-of-atherosclerosis-in-ldl-receptor%C3%A2-deficient-mice
#17
Jianzhen Lv, Wen Xiong, Tiantian Lei, Hailian Wang, Minghan Sun, Erwei Hao, Zhiping Wang, Xiaoqi Huang, Shaoping Deng, Jiagang Deng, Yi Wang
Previous studies have demonstrated that regulatory T cells (Tregs) are pivotal in the regulation of T cell‑mediated immune responses in atherosclerosis, a chronic autoimmune‑like disease. In the authors' previous studies, it was demonstrated that amygdalin ameliorated atherosclerosis by the regulation of Tregs in apolipoprotein E‑deficient (ApoE‑/‑) mice. Therefore, the aim of the present study was to investigate the therapeutic effect of amygdalin on low‑density lipoprotein (LDL) receptor deficient (LDLR‑/‑) mice, and to examine its immune regulatory function by the stimulation of Tregs...
September 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28972541/camkii%C3%AE-suppresses-an-efferocytosis-pathway-in-macrophages-and-promotes-atherosclerotic-plaque-necrosis
#18
Amanda C Doran, Lale Ozcan, Bishuang Cai, Ze Zheng, Gabrielle Fredman, Christina C Rymond, Bernhard Dorweiler, Judith C Sluimer, Joanne Hsieh, George Kuriakose, Alan R Tall, Ira Tabas
Atherosclerosis is the underlying etiology of cardiovascular disease, the leading cause of death worldwide. Atherosclerosis is a heterogeneous disease in which only a small fraction of lesions lead to heart attack, stroke, or sudden cardiac death. A distinct type of plaque containing large necrotic cores with thin fibrous caps often precipitates these acute events. Here, we show that Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ) in macrophages plays a major role in the development of necrotic, thin-capped plaques...
October 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28970916/tailored-theranostic-apolipoprotein-e3-porphyrin-lipid-nanoparticles-target-glioblastoma
#19
M A Rajora, L Ding, M Valic, W Jiang, M Overchuk, J Chen, G Zheng
The development of curative glioblastoma treatments and tumour-specific contrast agents that can overcome the blood-brain barrier (BBB) and infiltrative tumour morphology remains a challenge. Apolipoprotein E3 (apoE3) is a high density lipoprotein apolipoprotein that chaperones the transcytosis of nanoparticles across the BBB, and displays high-affinity binding with the low density lipoprotein receptor (LDLR), a cell-surface receptor overexpressed by glioblastoma cells. This LDLR overexpression and apoE3 binding capacity was exploited for the development of glioblastoma-targeted porphyrin-lipid apoE3 lipid nanoparticles (pyE-LNs) with intrinsic theranostic properties...
August 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28970592/a-therapeutic-peptide-vaccine-against-pcsk9
#20
Yajie Pan, Yanzhao Zhou, Hailang Wu, Xiao Chen, Xiajun Hu, Hongrong Zhang, Zihua Zhou, Zhihua Qiu, Yuhua Liao
Vaccination provides a promising approach for treatment of hypercholesterolemia and improvement in compliance. In this study, the appropriate virus-like particle (VLP)-peptide vaccines targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) were screened. The screening criteria of target peptides were as follows: (1) located in catalytic domain of PCSK9, or regulating the binding of PCSK9 and LDL receptors (LDLR); (2) having low/no-similarity when matched with the host proteome; (3) possessing ideal antigenicity and hydrophilicity; (4) including the functional mutation site of PCSK9...
October 2, 2017: Scientific Reports
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