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Lipid cholesterol metabolism atherosclerosis

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https://www.readbyqxmd.com/read/28549500/greater-preclinical-atherosclerosis-in-treated-monogenic-familial-hypercholesterolemia-vs-polygenic-hypercholesterolemia
#1
Mahtab Sharifi, Elizabeth Higginson, Sven Bos, Angela Gallivan, Darren Harvey, Ka Wah Li, Amali Abeysekera, Angela Haddon, Helen Ashby, Kate E Shipman, Jackie A Cooper, Marta Futema, Jeanine E Roeters van Lennep, Eric J G Sijbrands, Mourad Labib, Devaki Nair, Steve E Humphries
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a common inherited disorder of low density lipoprotein-cholesterol (LDL-C) metabolism. It is associated with higher risk of premature coronary heart disease. Around 60% of patients with a clinical diagnosis of FH do not have a detectable mutation in the genes causing FH and are most likely to have a polygenic cause for their raised LDL-C. We assessed the degree of preclinical atherosclerosis in treated patients with monogenic FH versus polygenic hypercholesterolemia...
May 13, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28546220/activation-of-adiponectin-receptor-regulates-proprotein-convertase-subtilisin-kexin-type-9-expression-and-inhibits-lesions-in-apoe-deficient-mice
#2
Lei Sun, Xiaoxiao Yang, Qi Li, Peng Zeng, Ying Liu, Lipei Liu, Yuanli Chen, Miao Yu, Chuanrui Ma, Xiaoju Li, Yan Li, Rongxin Zhang, Yan Zhu, Qing Robert Miao, Jihong Han, Yajun Duan
OBJECTIVE: The reduced adiponectin levels are associated with atherosclerosis. Adiponectin exerts its functions by activating adiponectin receptor (AdipoR). Proprotein convertase subtilisin kexin type 9 (PCSK9) degrades LDLR protein (low-density lipoprotein receptor) to increase serum LDL-cholesterol levels. PCSK9 expression can be regulated by PPARγ (peroxisome proliferator-activated receptor γ) or SREBP2 (sterol regulatory element-binding protein 2). The effects of AdipoR agonists on PCSK9 and LDLR expression, serum lipid profiles, and atherosclerosis remain unknown...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28546217/increased-hepatic-expression-of-endothelial-lipase-inhibits-cholesterol-diet-induced-hypercholesterolemia-and-atherosclerosis-in-transgenic-rabbits
#3
Chuan Wang, Kazutoshi Nishijima, Shuji Kitajima, Manabu Niimi, Haizhao Yan, Yajie Chen, Bo Ning, Fumikazu Matsuhisa, Enqi Liu, Jifeng Zhang, Y Eugene Chen, Jianglin Fan
OBJECTIVE: Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. APPROACH AND RESULTS: We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates...
May 25, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28538111/cardiovascular-and-metabolic-effects-of-angptl3-antisense-oligonucleotides
#4
Mark J Graham, Richard G Lee, Teresa A Brandt, Li-Jung Tai, Wuxia Fu, Raechel Peralta, Rosie Yu, Eunju Hurh, Erika Paz, Bradley W McEvoy, Brenda F Baker, Nguyen C Pham, Andres Digenio, Steven G Hughes, Richard S Geary, Joseph L Witztum, Rosanne M Crooke, Sotirios Tsimikas
Background Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. Methods We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1...
May 24, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28534127/genetics-of-triglycerides-and-the-risk-of-atherosclerosis
#5
REVIEW
Jacqueline S Dron, Robert A Hegele
PURPOSE OF REVIEW: Plasma triglycerides are routinely measured with a lipid profile, and elevated plasma triglycerides are commonly encountered in the clinic. The confounded nature of this trait, which is correlated with numerous other metabolic perturbations, including depressed high-density lipoprotein cholesterol (HDL-C), has thwarted efforts to directly implicate triglycerides as causal in atherogenesis. Human genetic approaches involving large-scale populations and high-throughput genomic assessment under a Mendelian randomization framework have undertaken to sort out questions of causality...
July 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#6
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28486149/dietary-supplementation-with-long-chain-monounsaturated-fatty-acid-isomers-decreases-atherosclerosis-and-alters-lipoprotein-proteomes-in-ldlr-mice
#7
Zhi-Hong Yang, Scott M Gordon, Denis Sviridov, Shuibang Wang, Robert L Danner, Milton Pryor, Boris Vaisman, Yuka Shichijo, Nobushige Doisaki, Alan T Remaley
BACKGROUND AND AIMS: Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models. It is not clear, however, how individual LCMUFA isomers may act on atherosclerosis. METHODS: In the present study, we used saury fish oil-derived concentrates enriched in either C20:1 or C22:1 isomer fractions to investigate their individual effect on atherosclerosis and lipoprotein metabolism...
April 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28485501/mir-34a-targets-hdac1-regulated-h3k9-acetylation-on-lipid-accumulation-induced-by-homocysteine-in-foam-cells
#8
Qingguo Zhao, Shuqiang Li, Nan Li, Xiaoling Yang, Shengchao Ma, Anning Yang, Hui Zhang, Songhao Yang, Caiyan Mao, Lingbo Xu, Tingting Gao, Xiaoming Yang, Huiping Zhang, Yideng Jiang
Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE(-/-) mice fed with high methionine diet, whereas miR-34a expression was inhibited...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#9
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28435982/-changes-in-biological-functions-of-high-density-lipoprotein-after-abnormal-modification
#10
Hang Qu, Yang Yu, Shu-Cun Qin, Guo-Hua Song
High-density lipoprotein (HDL) is composed of apolipoproteins, lipids and functional proteins. HDL protects against atherosclerosis (AS) by reverse cholesterol transport (RCT). HDL inhibits the lipid oxidation, inflammation and restores endothelial function. During systemic inflammation or metabolic disorders, HDL can be modified abnormally and converted to a dysfunctional type, which results in the loss of anti-inflammatory factors including apolipoprotein A-I (apoA-I), paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH), and gains of pro-inflammatory factors such as serum amyloid A (SAA), triglyceride (TG) and oxidative lipid...
April 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28431321/atherogenicity-of-amino-acids-in-the-lipid-laden-macrophage-model-system-in-vitro-and-in-atherosclerotic-mice-a-key-role-for-triglyceride-metabolism
#11
Oren Rom, Claudia Grajeda-Iglesias, Mahmoud Najjar, Niroz Abu-Saleh, Nina Volkova, Dalit Esther Dar, Tony Hayek, Michael Aviram
Atherosclerosis-related research has focused mainly on the effects of lipids on macrophage foam cell formation and atherogenesis, whereas the role of amino acids (AAs) was understudied. The current study aimed to identify anti- or pro-atherogenic AA in the macrophage model system and to elucidate the underlying metabolic and molecular mechanisms. J774A.1 cultured macrophages were treated with increasing concentrations of each 1 of the 20 AAs. Macrophage atherogenicity was assessed in terms of cellular toxicity, generation of reactive oxygen species (ROS) and cellular cholesterol or triglyceride content...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#12
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/28400053/proprotein-convertase-furin-pcsk3-and-atherosclerosis-new-insights-and-potential-therapeutic-targets
#13
REVIEW
Kun Ren, Ting Jiang, Xi-Long Zheng, Guo-Jun Zhao
Furin, a member of the mammalian proprotein convertases family, can promote the proteolytic maturation of proproteins. It is known that furin is predominantly present in certain cell types of human atherosclerotic lesions and neointima in animal models, including vascular smooth muscle cells, endothelial cells and mononuclear inflammatory cells. Evidence suggests that furin participates in the initiation and progression of atherosclerosis through regulation of lipid and cholesterol metabolism, inflammatory response, blood pressure and the formation of atherosclerotic lesions...
April 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28391892/current-smokers-with-hyperlipidemia-lack-elevated-pre%C3%AE-1-high-density-lipoprotein-concentrations
#14
Yuki Nagao, Satoshi Hirayama, Mika Kon, Kenta Sasamoto, Masami Sugihara, Akiko Hirayama, Miwa Isshiki, Utako Seino, Osamu Miyazaki, Takashi Miida
BACKGROUND: Preβ1-high-density lipoprotein (HDL) is an efficient acceptor of cell-derived free cholesterol, which is converted into lipid-rich HDL by lecithin-cholesterol acyltransferase. Previous studies have shown that preβ1-HDL is significantly higher in individuals with hyperlipidemia. Preβ1-HDL concentrations may be altered in smokers, who are at high risk for atherosclerosis. OBJECTIVE: The aim of the present study was to investigate the effect of smoking on preβ1-HDL concentrations...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28391883/childhood-adult-onset-lysosomal-acid-lipase-deficiency-a-serious-metabolic-and-vascular-phenotype-beyond-liver-disease-four-new-pediatric-cases
#15
Pierre Poinsot, Sophie Collardeau Frachon, Lioara Restier, André Sérusclat, Mathilde Di Filippo, Sybil Charrière, Philippe Moulin, Alain Lachaux, Noel Peretti
BACKGROUND: The childhood/adult-onset lysosomal acid lipase deficiency (LALD; late-onset LALD) is a rare genetic disease. Children present severe fatty liver disease with early cirrhosis. Before enzyme replacement therapy, statins were the standard treatment to improve the severe dyslipidemia. However, late-onset LALD should be considered as a systemic metabolic disease: chronic hyper-low-density lipoprotein and hypo-high-density lipoprotein cholesterolemia induces early atherosclerosis in addition to the liver morbidity...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28380440/monoglyceride-lipase-deficiency-affects-hepatic-cholesterol-metabolism-and-lipid-dependent-gut-transit-in-apoe-mice
#16
Nemanja Vujic, Melanie Korbelius, Christina Leopold, Madalina Duta-Mare, Silvia Rainer, Stefanie Schlager, Madeleine Goeritzer, Dagmar Kolb, Thomas O Eichmann, Clemens Diwoky, Andreas Zimmer, Robert Zimmermann, Achim Lass, Branislav Radovic, Dagmar Kratky
Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28367087/expression-of-sterol-regulatory-element-binding-proteins-in-epicardial-adipose-tissue-in-patients-with-coronary-artery-disease-and-diabetes-mellitus-preliminary-study
#17
Luis M Pérez-Belmonte, Inmaculada Moreno-Santos, Fernando Cabrera-Bueno, Gemma Sánchez-Espín, Daniel Castellano, Miguel Such, María G Crespo-Leiro, Fernando Carrasco-Chinchilla, Luis Alonso-Pulpón, Miguel López-Garrido, Amalio Ruiz-Salas, Víctor M Becerra-Muñoz, Juan J Gómez-Doblas, Eduardo de Teresa-Galván, Manuel Jiménez-Navarro
Objectives: Sterol regulatory element-binding proteins (SREBP) genes are crucial in lipid biosynthesis and cardiovascular homeostasis. Their expression in epicardial adipose tissue (EAT) and their influence in the development of coronary artery disease (CAD) and type-2 diabetes mellitus remain to be determined. The aim of our study was to evaluate the expression of SREBP genes in EAT in patients with CAD according to diabetes status and its association with clinical and biochemical data. Methods: SREBP-1 and SREBP-2 mRNA expression levels were measured in EAT from 49 patients with CAD (26 with diabetes) and 23 controls without CAD or diabetes...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28365054/lipid-metabolism-and-emerging-targets-for-lipid-lowering-therapy
#18
REVIEW
Daniel Gaudet, Jean-Philippe Drouin-Chartier, Patrick Couture
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide, and dyslipidemia constitutes a major risk factor for CVD and premature atherosclerosis. Therapies to reduce the plasma levels of atherogenic lipoproteins are well established interventions that decrease CVD risk. However, treatment of dyslipidemia with the most widely used lipid-lowering drugs (ie, statins and ezetimibe) often fails to protect a significant proportion of patients from cardiovascular risk. The development of several novel therapies to treat lipid-related disorders and their associated risks is ongoing and includes the following: (1) reducing plasma levels of atherogenic lipoproteins using proprotein convertase subtilisin/kexin type 9 inhibitors, antisense inhibitors of Apolipoprotein (Apo)(a), microsomal triglyceride transfer protein inhibitors, antisense oligonucleotides of ApoB for inhibiting very low-density lipoprotein production, and inhibitors of angiopoietin-like protein 3 or ApoC-III for triglyceride-rich lipoprotein management upstream of low-density lipoprotein production as well as gene replacement therapy to improve low-density lipoprotein and triglyceride-rich lipoprotein clearance; and (2) emerging therapies that target high-density lipoprotein (HDL) and reverse cholesterol transport using cholesteryl ester transfer protein inhibitors, HDL peptide mimetics, and autologous infusion of pre-β HDLs...
January 16, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28345767/nlrp3-inflammasome-its-regulation-and-involvement-in-atherosclerosis
#19
REVIEW
Zahra Hoseini, Fatemeh Sepahvand, Bahman Rashidi, Amirhossein Sahebkar, Aria Masoudifar, Hamed Mirzaei
Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1β and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1β, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome...
March 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28342064/hdl-cholesterol-reappraisal-of-its-clinical-relevance
#20
REVIEW
Winfried März, Marcus E Kleber, Hubert Scharnagl, Timotheus Speer, Stephen Zewinger, Andreas Ritsch, Klaus G Parhofer, Arnold von Eckardstein, Ulf Landmesser, Ulrich Laufs
BACKGROUND: While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted...
March 24, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
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