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HMG coA reductase

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https://www.readbyqxmd.com/read/29325849/coagonist-of-glp-1-and-glucagon-decreases-liver-inflammation-and-atherosclerosis-in-dyslipidemic-condition
#1
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Dhreerendra Pandey, Hiren Patel, Ramchandra Ranvir, Shekhar Kadam, Dipam Patel, Rajesh Bahekar, Mukul Jain
Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and glucagon are under clinical investigation for the treatment of obesity and diabetes. Earlier, we have observed that coagonist reduced circulating and hepatic lipids, independent of its anorexic effects. Here, we investigated the role of coagonist of GLP-1 and glucagon receptors in complications of diet-induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of GLP-1 and glucagon receptors (75 and 150 μg/kg)...
January 8, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29321515/nationwide-survey-on-cerebrotendinous-xanthomatosis-in-japan
#2
Yoshiki Sekijima, Shingo Koyama, Tsuneaki Yoshinaga, Masayoshi Koinuma, Yuji Inaba
Cerebrotendinous xanthomatosis (CTX) is likely to be underdiagnosed and precise epidemiological characteristics of CTX are largely unknown as knowledge on the disorder is based mainly on case reports. We conducted a nationwide survey on CTX to elucidate the frequency, clinical picture, and molecular biological background of Japanese CTX patients. In this first Japanese nationwide survey on CTX, 2541 questionnaires were sent to clinical departments across Japan. A total of 1032 (40.6%) responses were returned completed for further analysis...
January 10, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29310688/effect-of-eicosapentaenoic-acid-docosahexaenoic-acid-on-coronary-high-intensity-plaques-detected-with-non-contrast-t1-weighted-imaging-the-aquamarine-epa-dha-study-study-protocol-for-a-randomized-controlled-trial
#3
Kazuhiro Nakao, Teruo Noguchi, Yasuhide Asaumi, Yoshiaki Morita, Tomoaki Kanaya, Masashi Fujino, Hayato Hosoda, Shuichi Yoneda, Shoji Kawakami, Toshiyuki Nagai, Kensaku Nishihira, Takahiro Nakashima, Reon Kumasaka, Tetsuo Arakawa, Fumiyuki Otsuka, Michio Nakanishi, Yu Kataoka, Yoshio Tahara, Yoichi Goto, Haruko Yamamoto, Toshimitsu Hamasaki, Satoshi Yasuda
BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals...
January 8, 2018: Trials
https://www.readbyqxmd.com/read/29288118/statins-reduce-the-expressions-of-tim-3-on-nk-cells-and-nkt-cells-in-atherosclerosis
#4
Na Zhang, Min Zhang, Ru-Tao Liu, Peng Zhang, Chun-Lin Yang, Long-Tao Yue, Heng Li, Yong-Kang Li, Rui-Sheng Duan
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidences showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3(Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control...
December 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29278865/simvastatin-activates-single-skeletal-ryr1-channels-but-exerts-more-complex-regulation-of-the-cardiac-ryr2-isoform
#5
Elisa Venturi, Chris Lindsay, Sabine Lotteau, Zhaokang Yang, Emma Steer, Katja Witschas, Abigail D Wilson, James R Wickens, Angela J Russell, Derek Steele, Sarah Calaghan, Rebecca Sitsapesan
BACKGROUND AND PURPOSE: Statins are amongst the most widely prescribed drugs for those at risk of cardiovascular disease, lowering cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Although effective in prevention of cardiovascular disease, statin use is associated with muscle weakness, myopathies and, in rare cases, fatal rhabdomyolysis. As simvastatin, a commonly prescribed statin, can promote Ca2+ release from sarcoplasmic reticulum (SR) vesicles, we investigated if simvastatin could directly activate skeletal (RyR1) and cardiac (RyR2) ryanodine receptors...
December 26, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29278293/green-tea-polyphenol-egcg-alleviates-metabolic-abnormality-and-fatty-liver-by-decreasing-bile-acid-and-lipid-absorption-in-mice
#6
Jinbao Huang, Simin Feng, Anna Liu, Zhuqing Dai, Hong Wang, Kenneth Reuhl, Wenyun Lu, Chung S Yang
SCOPE: The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been shown to ameliorate metabolic abnormalities and fatty liver. The present study investigated the mechanisms of actions of EGCG on bile acid homeostasis and lipid metabolism. METHODS: Male C57BL/6J mice were fed a low-fat diet, a high-fat western-style diet or a high-fat western-style diet containing 0.32% EGCG. The effects of the treatments on biochemical parameters, gene expression and lipidomics were analyzed...
December 26, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29276295/cholesterol-ester-transfer-protein-inhibitor-review
#7
Jerry Hu, Scot Walker
Treatment of blood cholesterol is part of a strategy to lower atherosclerotic cardiovascular (ASCVD) risk. While use of HMG-CoA reductase inhibitors to modify cholesterol levels is the primary means of lowering the risk of an ASCVD event, residual risk remains. A new strategy being investigated is the use of cholesterol ester transfer protein (CETP) inhibitors to raise the levels of high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C). While initial large-scale studies demonstrated no reduction of cardiovascular events, one CETP inhibitor, anacetrapib, has demonstrated a reduction in cardiovascular events in the REVEAL trial...
October 2017: Hospital Pharmacy
https://www.readbyqxmd.com/read/29275178/central-administration-of-coagonist-of-glp-1-and-glucagon-receptors-improves-dyslipidemia
#8
Vishal Patel, Amit Joharapurkar, Samadhan Kshirsagar, Brijesh Sutariya, Maulik Patel, Hiren Patel, Dheerendra Pandey, Dipam Patel, Rajesh Bahekar, Mukul Jain
Coagonists of Glucagon-like peptide-1 (GLP-1) and glucagon receptors are under clinical investigation for treatment of obesity associated with diabetes. In addition to their role in glucose homeostasis, GLP-1 and glucagon modulate lipid metabolism. In this study, we have investigated the role of central GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) activation in regulation of lipid metabolism in cholesterol-fed hamsters. Hamsters were treated with coagonist alone (0.3 μg) or in combination with either GLP-1R antagonist (0...
December 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29274033/supplementation-with-an-insoluble-fiber-obtained-from-carob-pod-ceratonia-siliqua-l-rich-in-polyphenols-prevents-dyslipidemia-in-rabbits-through-sirt1-pgc-1%C3%AE-pathway
#9
María Valero-Muñoz, Sandra Ballesteros, Baltasar Ruiz-Roso, Lourdes Pérez-Olleros, Beatriz Martín-Fernández, Vicente Lahera, Natalia de Las Heras
PURPOSE: To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver. METHODS: Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group)...
December 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29237679/statin-effects-on-metabolic-profiles-data-from-the-prevend-it-prevention-of-renal-and-vascular-end-stage-disease-intervention-trial
#10
Daniel Kofink, Ruben N Eppinga, Wiek H van Gilst, Stephan J L Bakker, Robin P F Dullaart, Pim van der Harst, Folkert W Asselbergs
BACKGROUND: Statins lower cholesterol by inhibiting HMG-CoA reductase, the rate-limiting enzyme of the metabolic pathway that produces cholesterol and other isoprenoids. Little is known about their effects on metabolite and lipoprotein subclass profiles. We, therefore, investigated the molecular changes associated with pravastatin treatment compared with placebo administration using a nuclear magnetic resonance-based metabolomics platform. METHODS AND RESULTS: We performed metabolic profiling of 231 lipoprotein and metabolite measures in the PREVEND IT (Prevention of Renal and Vascular End-stage Disease Intervention Trial) study, a placebo-controlled randomized clinical trial designed to test the effects of pravastatin (40 mg once daily) on cardiovascular risk...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29224355/structural-features-and-domain-movements-controlling-substrate-binding-and-cofactor-specificity-in-class-ii-hmg-coa-reductase
#11
Bradley R Miller, Yan Kung
The key mevalonate pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) uses the cofactor NAD(P)H to reduce HMG-CoA to mevalonate in the production of countless metabolites and natural products. Although HMGR inhibition by statin drugs is well understood, several mechanistic details of HMGR catalysis remain unresolved, and the structural basis for the wide range in cofactor specificity for either NADH or NADPH among HMGRs from different organisms is also unknown. Here, we present crystal structures of HMGR from Streptococcus pneumoniae (SpHMGR) alongside kinetic data on the enzyme's cofactor preferences...
December 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/29199554/antioxidative-and-inhibitory-effects-of-the-fruiting-body-of-black-lingzhi-mushroom-amauroderma-rugosum-agaricomycetes-on-ldl-oxidation-and-hmg-coa-reductase-activity
#12
Chan Kam Seng, Noorlidah Abdullah, Norhaniza Aminudin
Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/29180648/csa13-inhibits-colitis-associated-intestinal-fibrosis-via-a-formyl-peptide-receptor-like-1-mediated-hmg-coa-reductase-pathway
#13
Chunlan Xu, Sally Ghali, Jiani Wang, David Q Shih, Christina Ortiz, Caroline C Mussatto, Elaine C Lee, Diana H Tran, Jonathan P Jacobs, Venu Lagishetty, Phillip Fleshner, Lori Robbins, Michelle Vu, Tressia C Hing, Dermot P B McGovern, Hon Wai Koon
Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature and antimicrobial function with antimicrobial peptide cathelicidin. As many functions of cathelicidin are mediated through formyl peptide receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human intestinal biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated intestinal fibrosis mouse model with the administration of CSA13 was used...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29173649/an-obesogenic-diet-enriched-with-blue-mussels-protects-against-weight-gain-and-lowers-cholesterol-levels-in-c57bl-6-mice
#14
Hitesh B Vaidya, Surendiran Gangadaran, Sukhinder K Cheema
Obesity is linked to several health complications, such as cardiovascular disease, insulin resistance, and hypertension. Dyslipidemia in obesity is one of the prime causes for health complications. We have previously shown that blue mussels (BM) are a rich source of omega (n)-3 polyunsaturated fatty acids (PUFA) and increase the mRNA expression of peroxisome-proliferator activated receptor and adiponectin, thereby inducing anti-obesity and insulin sensitizing effects in vitro. However, the in vivo effects of BM on obesity and metabolic regulation are not known...
October 2017: Nutrition Research
https://www.readbyqxmd.com/read/29167270/ubia-prenyltransferase-domain-containing-protein-1-modulates-hmg-coa-reductase-degradation-to-coordinate-synthesis-of-sterol-and-nonsterol-isoprenoids
#15
Marc M Schumacher, Dong-Jae Jun, Brittany M Johnson, Russell A DeBose-Boyd
UbiA prenyltransferase domain-containing protein-1 (UBIAD1) utilizes geranylgeranyl pyrophosphate (GGpp) to synthesize vitamin K2. We previously reported that sterols stimulate binding of UBIAD1 to endoplasmic reticulum (ER)-localized HMG CoA reductase. UBIAD1 binding inhibits sterol-accelerated, ER-associated degradation (ERAD) of reductase, one of several mechanisms for feedback control of this rate-limiting enzyme in the branched pathway that produces cholesterol and nonsterol isoprenoids such as GGpp. Accumulation of GGpp in ER membranes triggers release of UBIAD1 from reductase, permitting its maximal ERAD and ER-to-Golgi transport of UBIAD1...
November 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29165404/benefits-of-nut-consumption-on-insulin-resistance-and-cardiovascular-risk-factors-multiple-potential-mechanisms-of-actions
#16
REVIEW
Yoona Kim, Jennifer B Keogh, Peter M Clifton
Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM) and related cardiovascular disease (CVD). The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies...
November 22, 2017: Nutrients
https://www.readbyqxmd.com/read/29164519/atorvastatin-prevents-early-oxidative-events-and-modulates-inflammatory-mediators-in-the-striatum-following-intranasal-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-administration-in-rats
#17
Naiani F Marques, Adalberto A Castro, Gianni Mancini, Fernanda L Rocha, Adair R S Santos, Rui D Prediger, Andreza Fabro De Bem, Carla I Tasca
Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Parkinson's disease (PD) development. Here, we evaluated early events involved in the neurotoxicity induced by intranasal (i.n.) infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rats and the potential of atorvastatin to prevent these early toxic events...
November 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29162465/linoleic-acid-enhance-the-production-of-moncolin-k-and-red-pigments-in-monascus-ruber-by-activating-mokh-and-moka-and-by-accelerating-camp-pka-pathway
#18
Jing Huang, NanQing Liao, HaoMing Li
Monacolin K, an inhibitor of HMG-CoA reductase, is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus ruber. The mokH gene encoding Zn(II)2Cys6 binding protein and mokA gene encoding polyketide synthase are presumed to activate monacolin K production. In this study, linoleic acid could be a quorum sensing signaling molecule to increase monacolin K production in the cyclic AMP(cAMP)-protein kinase A(PKA) signaling pathway. Analysis of the PKA activity and the cAMP concentration shows that linoleic acid could increase cAMP concentration and activate PKA...
November 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29158265/topical-mevastatin-promotes-wound-healing-by-inhibiting-the-transcription-factor-c-myc-via-the-glucocorticoid-receptor-and-the-long-noncoding-rna-gas5
#19
Andrew P Sawaya, Irena Pastar, Olivera Stojadinovic, Sonja Lazovic, Stephen C Davis, Joel Gil, Robert S Kirsner, Marjana Tomic-Canic
Diabetic foot ulcers (DFU), a life-threatening complication of diabetes mellitus, have limited treatment options, often resulting in amputations. HMG-CoA reductase inhibitors such as statins are cholesterol-reducing agents that may provide a new therapeutic option. Statins target the cholesterol pathway and block the synthesis of the wound-healing inhibitors farnesyl pyrophosphate (FPP) and cortisol, ligands for the glucocorticoid receptor (GR). Here we demonstrate that the naturally occurring statin, mevastatin, reverses FPP's effects and promotes healing by using in vitro wound healing assays, human ex vivo and porcine in vivo wound models, and DFU tissue...
November 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29155848/an-electronic-health-record-based-model-predicts-statin-adherence-ldl-cholesterol-and-cardiovascular-disease-in-the-united-states-military-health-system
#20
Joseph E Lucas, Taylor C Bazemore, Celan Alo, Patrick B Monahan, Deepak Voora
HMG-CoA reductase inhibitors (or "statins") are important and commonly used medications to lower cholesterol and prevent cardiovascular disease. Nearly half of patients stop taking statin medications one year after they are prescribed leading to higher cholesterol, increased cardiovascular risk, and costs due to excess hospitalizations. Identifying which patients are at highest risk for not adhering to long-term statin therapy is an important step towards individualizing interventions to improve adherence. Electronic health records (EHR) are an increasingly common source of data that are challenging to analyze but have potential for generating more accurate predictions of disease risk...
2017: PloS One
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