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HMG-CoA reductase

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https://www.readbyqxmd.com/read/28820396/the-role-of-mtor-inhibitors-and-hmg-coa-reductase-inhibitors-on-young-and-old-endothelial-cell-functions-critical-for-re-endothelialisation-after-percutaneous-coronary-intervention-an-in-vitro-study
#1
K Korybalska, E Kawka, A Breborowicz, J Witowski
Percutaneous coronary intervention (PCI) has become a standard treatment in patients with acute coronary syndrome. However, it is associated with endothelial cell denudation, which may predispose to in-stent thrombosis and restenosis. Pharmacological methods which prevent restenosis can delay post-PCI re-endothelialisation. We have therefore examined how atorvastatin (HMG-CoA reductase inhibitor), sirolimus and everolimus (mTOR inhibitors) affect young and old endothelial cell functions which are responsible for wound healing after PCI...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28812326/effect-of-dietary-components-from-antarctic-krill-on-atherosclerosis-in-apoe-deficient-mice
#2
Cinzia Parolini, Bodil Bjorndal, Marco Busnelli, Stefano Manzini, Giulia S Ganzetti, Federica Dellera, Marie Ramsvik, Inge Bruheim, Rolf Kristian Berge, Giulia Chiesa
SCOPE: Antarctic krill is a great source of n-3 fatty acids and high-quality proteins. Aim of the study was to evaluate the effect of Antarctic krill components on plasma lipids and atherosclerosis development. METHODS AND RESULTS: Sixty apoEKO mice were divided into four groups and fed Western diet (CONTROL) or Western-like diets, differing for protein or fat content. Specifically, casein or fat in CONTROL was partially replaced by krill proteins (PRO), krill oil (KRILL OIL), or both (KRILL OIL+PRO)...
August 15, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28808476/bark-extracts-of-ceylon-cinnamon-possess-antilipidemic-activities-and-bind-bile-acids-in-vitro
#3
Walimuni Prabhashini Kaushalya Mendis Abeysekera, Sirimal Premakumara Galbada Arachchige, Wanigasekera Daya Ratnasooriya
Ethanol (95%) and dichloromethane : methanol (1 : 1) bark extracts of authenticated Ceylon cinnamon were investigated for range of antilipidemic activities (ALA): HMG-CoA reductase, lipase, cholesterol esterase, and cholesterol micellization inhibitory activities and bile acids binding in vitro. Individual compounds in bark extracts were also evaluated. Bark extracts showed ALA in all the assays studied. The IC50 (μg/mL) values ranged within 153.07 ± 8.38-277.13 ± 32.18, 297.57 ± 11.78-301.09 ± 4...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28796249/rho-inhibition-by-lovastatin-affects-apoptosis-and-dsb-repair-of-primary-human-lung-cells-in-vitro-and-lung-tissue-in-vivo-following-fractionated-irradiation
#4
Verena Ziegler, Christian Henninger, Ioannis Simiantonakis, Marcel Buchholzer, Mohammad Reza Ahmadian, Wilfried Budach, Gerhard Fritz
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28771594/patients-experiencing-statin-induced-myalgia-exhibit-a-unique-program-of-skeletal-muscle-gene-expression-following-statin-re-challenge
#5
Marshall B Elam, Gipsy Majumdar, Khyobeni Mozhui, Ivan C Gerling, Santiago R Vera, Hannah Fish-Trotter, Robert W Williams, Richard D Childress, Rajendra Raghow
Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls...
2017: PloS One
https://www.readbyqxmd.com/read/28745862/glcnac-conjugated-atorvastatin-with-enhanced-water-solubility-and-cellular-internalization
#6
Xinfu Zhang, Xiaofang Chen, Weiyu Zhao, Chunxi Zeng, Xiao Luo, Wenqing Li, Bin Li, Justin Jiang, Yizhou Dong
Targeting ligands facilitate cell specific drug delivery and improve pharmaceutical properties. Herein, we designed two ligand drug conjugates by conjugating GlcNAc (N-acetylglucosamine) with atorvastatin. These two conjugates, termed G-AT and G-K-AT, exhibited enhanced water solubility and cellular uptake. Moreover, both G-AT and G-K-AT were able to release atorvastatin and consequently achieve significant inhibition against 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase.
August 16, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28732362/acute-atorvastatin-treatment-restores-the-cardioprotective-effects-of-ischemic-postconditioning-in-hyperlipidemic-rats
#7
Tao Sun, Hong-Ju Zhang, Chayakrit Krittanawong, Su Wang, Ying Tao, Zhao Li, Qiancheng Yin, Donghua Zhang, Qian Wang, Ji Huang, Jingmei Zhang, Zhizhong Li, Yutong Cheng
BACKGROUND: Ischemic Postconditioning (IPC) reduces ischemia/reperfusion (I/R) injury under normal conditions. HMG-CoA reductase inhibitors (statins), which inhibit the synthesis of mevalonate, can interfere with the cardioprotective effect of IPC. However, the beneficial role of IPC in hyperlipidemic patients, post-acute administration of statins remains unknown. This study was to determine if acute administration of atorvastatin affect the infarct size-limiting effect of IPC in hyperlipidemic rats...
July 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28731315/hypocholesterolemic-activity-of-cornelian-cherry-cornus-mas-l-fruits
#8
Fatemeh Hosseinpour, Tahoora Shomali, Mahmoud Rafieian-Kopaei
Background Lipid profile disturbances are important risk factors for cardiovascular events in patients with diabetes mellitus and finding safe and multifaceted agents is persuaded in this regard. This study aimed to evaluate the effect of cornelian cherry dried powder (CCDP) on serum lipid profile as well as liver antioxidant capacity, HMG-CoA reductase level and activity, and LDL receptor level in streptozotocin-induced diabetic rats. Methods Forty-eight male adult Wistar rats were randomly allocated into eight equal groups and were treated for 4 weeks as follows: negative control (normal rats, basic diet); positive control (diabetic rats, basic diet), T1 to T4 groups: diabetic rats fed with basic diet containing 0...
June 1, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28729731/anti-asthmatic-effect-of-pitavastatin-through-aerosol-inhalation-is-associated-with-cd4-cd25-foxp3-t-cells-in-an-asthma-mouse-model
#9
Songquan Wu, Ruhui Yang, Guangli Wang
Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl-CoA (HMG-A) reductase, and studies have shown that statins also have anti-inflammatory and immunomodulatory properties. The purpose of this study was to investigate the anti-asthmatic effects of pitavastatin, a type of statin, in an asthma mouse model. Mice were sensitized and challenged with ovalbumin (OVA) to establish the asthma model. These mice were then treated with inhaled pitavastatin (5 mg/kg) or dexamethasone (2 mg/kg), the latter of which served as a positive control...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729172/ascorbic-acid-supplementation-partially-prevents-the-delayed-reproductive-development-in-juvenile-male-rats-exposed-to-rosuvastatin-since-prepuberty
#10
Gabriel Adan Araújo Leite, Thamiris Moreira Figueiredo, Marciana Sanabria, Ana Flávia Mota Gonçalves Dias, Patrícia Villela E Silva, Airton da Cunha Martins Junior, Fernando Barbosa Junior, Wilma De Grava Kempinas
Dyslipidemias are occurring earlier in the population due to the increase of obesity and bad eating habits. Rosuvastatin inhibits the enzyme HMG-CoA reductase, decreasing total cholesterol. Ascorbic acid is an important antioxidant compound for male reproductive system. This study aimed to evaluate whether ascorbic acid supplementation may prevent the reproductive damage provoked by rosuvastatin administration at prepuberty. Male pups were distributed into six experimental groups that received saline solution 0...
July 18, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28720969/quantification-of-phenolics-in-syzygium-cumini-seed-and-their-modulatory-role-on-tertiary-butyl-hydrogen-peroxide-induced-oxidative-stress-in-h9c2-cell-lines-and-key-enzymes-in-cardioprotection
#11
H P Syama, A D Arya, R Dhanya, P Nisha, A Sundaresan, E Jacob, P Jayamurthy
The study quantified the major phenolics in different fractions of Syzygium cumini seeds and evaluated their cardioprotective efficacy. Gallic acid, ellagic acid, cinnamic acid, quercetin, syringic acid and ferulic acid were the major polyphenols present in different fractions of Syzygium cumini seeds. The cardioprotective effect of Syzygium cumini seed fractions in modulating angiotensin converting enzyme (ACE), HMG-CoA reductase, LDL oxidation and tertiary butyl hydrogen peroxide (TBHP) induced oxidative stress in H9c2 cardiac cell lines were investigated...
June 2017: Journal of Food Science and Technology
https://www.readbyqxmd.com/read/28700897/a-systematic-comparison-of-clinically-viable-nanomedicines-targeting-hmg-coa-reductase-in-inflammatory-atherosclerosis
#12
Amr Alaarg, Max L Senders, Aida Varela-Moreira, Carlos Pérez-Medina, Yiming Zhao, Jun Tang, Francois Fay, Thomas Reiner, Zahi A Fayad, Wim E Hennink, Josbert M Metselaar, Willem J M Mulder, Gert Storm
Atherosclerosis is a leading cause of worldwide morbidity and mortality whose management could benefit from novel targeted therapeutics. Nanoparticles are emerging as targeted drug delivery systems in chronic inflammatory disorders. To optimally exploit nanomedicines, understanding their biological behavior is crucial for further development of clinically relevant and efficacious nanotherapeutics intended to reduce plaque inflammation. Here, three clinically relevant nanomedicines, i.e., high-density lipoprotein ([S]-HDL), polymeric micelles ([S]-PM), and liposomes ([S]-LIP), that are loaded with the HMG-CoA reductase inhibitor simvastatin [S], were evaluated in the apolipoprotein E-deficient (Apoe(-/-)) mouse model of atherosclerosis...
July 9, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28692940/betulinic-acid-and-fluvastatin-exhibits-synergistic-effect-on-toll-like-receptor-4-mediated-anti-atherogenic-mechanism-in-type-ii-collagen-induced-arthritis
#13
Limi Elizabeth Mathew, Vrinda Rajagopal, Helen A
Cardiovascular disease (CVD) is a major problem during rheumatoid arthritis which leads to morbidity and mortality in arthritic patients. So the present study emphasizes combinatorial effect of Betulinic acid, a triterpenoid and fluvastatin, an HMG CoA reductase inhibitor on atherogenesis during arthritis. Arthritis was induced by bovine type II collagen dissolved in 0.01M acetic acid at a concentration of 4mg/mL and emulsified in equal volume of incomplete Freund's adjuvant. Betulinic acid (2mg/kg) and fluvastatin (5mg/kg) alone and in combination was administered orally from day 14 to 60...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28691428/stat-proteins-as-intracellular-regulators-of-resistance-to-myocardial-injury-in-context-of-cardiac-remodeling-and-targeting-for-therapy
#14
REVIEW
Andrzej Wincewicz, Stanislaw Sulkowski
Roles of STAT (signal transducers and activators of transcription) proteins are widely discussed in relation to other agents like IFN-γ that are involved in cardiovascular diseases. STAT3 protects cardiomyocytes during endotoxic shock and ischemia and prolongs survival of these cells by activation of antiapoptotic genes like bcl-2 and c-fos. Moreover, IL-6 dependent expression of STAT3 probably is responsible for hypertrophy of cardiomyocytes. On the contrary STAT1 mediates cell death by induction of caspase-1...
June 27, 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28690119/cholesterol-lowering-effect-of-aralia-elata-miq-seem-via-the-activation-of-srebp-2-and-the-ldl-receptor
#15
Kyung-A Hwang, Yu-Jin Hwang, Jin Song
BACKGROUND: Hyperlipidemia causes arteriosclerosis, a risk factor for coronary heart disease. Prevention of hyperlipidemia by improving dietary habits has recently attracted attention. In this regard, we investigated whether Aralia elata (Miq.) Seem (AE) extract inhibits hepatic cholesterol accumulation and modulate the cellular signaling pathway. METHODS: To determine AE's cholesterol regulating mechanism, we measured cholesterol level, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol regulating-related gene expression in HepG2 cells and in high-fat diet (HFD)-induced mice using ELISA and RT-PCR assay...
July 6, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28684216/evaluation-of-dna-damage-in-wistar-rat-tissues-with-hyperlipidemia-induced-by-tyloxapol
#16
Joubert Aires de Sousa, Patrícia Pereira, Mariangela da Costa Allgayer, Norma Possa Marroni, Alexandre de Barros Falcão Ferraz, Jaqueline Nascimento Picada
Hyperlipidemia is characterized by high levels of plasma triglycerides and LDL-cholesterol, accompanied by reduced HDL-cholesterol levels, and is often associated with an increased risk of cardiovascular diseases. However, few studies have shown the effects of hyperlipidemia on genomic stability. The aim of this study was to evaluate DNA damage provided by tyloxapol induced hyperlipidemia. Tyloxapol, a non-ionic surfactant, which increases the activity of the enzyme HMG-CoA reductase and decreases clearance of lipoproteins, was used to induce hyperlipidemia in Wistar rats...
July 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28677744/simvastatin-ameliorates-ionizing-radiation-induced-apoptosis-in-the-thymus-by-activating-the-akt-sirtuin-1-pathway-in-mice
#17
Hong Yang, Fei Huang, Yulong Tao, Xinbin Zhao, Lina Liao, Xia Tao
Simvastatin is a HMG-CoA reductase inhibitor widely used to lower plasma cholesterol and to protect against cardiovascular risk factors. The aim of this study was to investigate whether simvastatin attenuates ionizing radiation-induced damage in the mouse thymus and to elucidate the possible mechanisms invovled. For this purpose, male C57BL/6J mice aged 6 weeks were used and exposed to 4 Gy 60Co γ-radiation with or without simvastatin (20 mg/kg/day, for 14 days). Apoptosis was determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay or transmission electron microscopy (TEM) examination...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28674251/co-administration-of-fluvastatin-and-cyp3a4-and-cyp2c8-inhibitors-may-increase-the-exposure-to-fluvastatin-in-carriers-of-cyp2c9-genetic-variants
#18
Yuji Mukai, Masayuki Narita, Erika Akiyama, Kanami Ohashi, Yasutaka Horiuchi, Yuka Kato, Takaki Toda, Anders Rane, Nobuo Inotsume
Fluvastatin, which is one of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins), is primarily metabolized by CYP2C9 and to a lesser extent by CYP3A4 and CYP2C8. Predictions of drug-drug interactions (DDI) are important for the safety of combination therapies with statins, in particular drugs that are metabolized by CYP3A4. Little information is available regarding drug interactions with fluvastatin. Since CYP2C9 is a polymorphic enzyme, we investigated the effect of DDI via CYP2C9, CYP3A4, and CYP2C8 on fluvastatin pharmacokinetics by using a validated prediction method in relation to CYP2C9 variants...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28673574/ldl-c-levels-in-older-people-cholesterol-homeostasis-and-the-free-radical-theory-of-ageing-converge
#19
Mark T Mc Auley, Kathleen M Mooney
The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28667245/a-screen-for-inducers-of-bhlh-activity-identifies-pitavastatin-as-a-regulator-of-p21-rb-phosphorylation-and-e2f-target-gene-expression-in-pancreatic-cancer
#20
Nicholas Villarino, Lia Signaevskaia, Jaco van Niekerk, Rachel Medal, Heejung Kim, Reyhaneh Lahmy, Kathleen Scully, Anthony Pinkerton, SangWun Kim, Andrew Lowy, Pamela Itkin-Ansari
The average survival for patients with Pancreatic Ductal Adenocarcinoma (PDA) is merely 6 months, underscoring the need for new therapeutic approaches. During PDA progression, pancreatic acinar cells lose activity of the ClassI/II bHLH factors that regulate quiescence. We previously found that promoting transcriptional activity of the Class I bHLH factor E47 in highly aggressive PDA cells induced stable growth arrest in vitro and in vivo. To translate these findings for clinical utility, we developed a high throughput screening platform to identify small molecule inducers of Class I/II bHLH activity...
June 21, 2017: Oncotarget
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