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Condition: Cholesterol

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Total 572 results found since Jan 2013.

Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway
Highlights: ► Lipophilic statin, simvastatin, triggers apoptosis in human breast cancer cells via JNK/CHOP/DR5 dependent signaling. ► Simvastatin blockage of mevalonate and geranylgeranyl pyrophosphate is critical for pro-death effect. ► Death Receptor 5 protein levels are upregulated by simvastatin and necessary for simvastatin-induced apoptosis.Abstract: Simvastatin (SVA) was shown to up-regulate expression of death receptor-5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and phosphorylated c-Jun N-terminal kinase (pJNK) in human breast cancer cell lines. siRNA knockdown of DR5, CHOP or JNK signif...
Source: Cancer Letters - December 7, 2012 Category: Cancer & Oncology Authors: Archana Gopalan, Weiping Yu, Bob G. Sanders, Kimberly Kline Tags: Research Articles Source Type: research

Chronic Intermittent Hypoxia Induces Atherosclerosis via Activation of Adipose Angiopoietin-like 4.
CONCLUSIONS: Hypoxia inducible factor 1-mediated increase in adipose Angptl4 and ensuing lipoprotein lipase inactivation may contribute to atherosclerosis in patients with sleep apnea. PMID: 23328524 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory and Critical Care Medicine - January 17, 2013 Category: Respiratory Medicine Authors: Drager LF, Yao Q, Hernandez KL, Shin MK, Bevans-Fonti S, Gay J, Sussan TE, Jun JC, Myers AC, Olivecrona G, Schwartz AR, Halberg N, Scherer PE, Semenza GL, Powell DR, Polotsky VY Tags: Am J Respir Crit Care Med Source Type: research

Manganese, ICAM-1, MCP-1, and Endothelial Cell Dysfunction Molecular Bases of Disease
This study examines the hypothesis that Mn2+ supplementation can reduce the markers/risk factors of endothelial dysfunction in type 2 diabetes. Human umbilical vein endothelial cells (HUVECs) were cultured with or without Mn2+ supplementation and then exposed to high glucose (HG, 25 mm) to mimic diabetic conditions. Mn2+ supplementation caused a reduction in monocyte adhesion to HUVECs treated with HG or MCP-1. Mn2+ also inhibited ROS levels, MCP-1 secretion, and ICAM-1 up-regulation in HUVECs treated with HG. Silencing studies using siRNA against MnSOD showed that similar results were observed in MnSOD knockdown HUVECs fo...
Source: Journal of Biological Chemistry - March 1, 2013 Category: Chemistry Authors: Burlet, E., Jain, S. K. Tags: Metabolism Source Type: research

Cross-talk between TLR4-MyD88-NF-{kappa}B and SCAP-SREBP2 pathways mediates macrophage foam cell formation
This study was designed to investigate cross-talk between TLR4-MyD88-NF-B and SCAP-SREBP2 pathways in macrophage foam cell formation. phorbol 12-myristate 13-acetate-activated THP-1 macrophages were transfected with negative control or MyD88 small interfering (si)RNA. Transfected cells were incubated with LPS in the absence or presence of LDL or IB kinase (IKK) inhibitor (BMS-345541). Intracellular cholesterol content was assessed. mRNA and protein expression of LDLR, HMG-CoAR, SCAP, and SREBP2 were examined by real-time RT-PCR and Western blot analysis. Intracellular translocation of SCAP in the organelles was detected by...
Source: AJP: Heart and Circulatory Physiology - March 15, 2013 Category: Cardiology Authors: Li, L.-C., Varghese, Z., Moorhead, J. F., Lee, C.-T., Chen, J.-B., Ruan, X. Z. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Particle-Payload Delivery Systems Sneak Drugs Past Cancer's Defenses
DNA, siRNA and miRNA can reprogram cancer cells - that is, if these nucleic acids could cross through the cell membrane. A University of Colorado Cancer Center study published in the journal Therapeutic Delivery shows that cholesterol "rafts" can shepherd genetic payloads into cancer cells. "There are many promising therapeutic applications for nucleic acids, but because they can't diffuse across cell membranes on their own, delivery to cancer cells has been a major challenge...
Source: Health News from Medical News Today - April 4, 2013 Category: Consumer Health News Tags: Cancer / Oncology Source Type: news

Tertiary-Butylhydroquinone Upregulates Expression of ATP-Binding Cassette Transporter A1 via Nuclear Factor E2-Related Factor 2/Heme Oxygenase-1 Signaling in THP-1 Macrophage-Derived Foam Cells.
Conclusions: Nrf2/HO-1 signaling is required for the regulation by tBHQ of ABCA1 expression and cholesterol efflux in macrophage-derived foam cells and an antiatherogenic role of tBHQ is suggested. PMID: 23739547 [PubMed - as supplied by publisher]
Source: Circulation Journal - June 5, 2013 Category: Cardiology Authors: Lu Q, Tang SL, Liu XY, Zhao GJ, Ouyang XP, Lv YC, He PP, Yao F, Chen WJ, Tang YY, Zhang M, Zhang DW, Yin K, Tang CK Tags: Circ J Source Type: research

HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome
Conclusion In this model of MS, statin treatment reverses myocardial remodelling and improves ventricular relaxation through AMPK-mediated anti-fibrotic effects.
Source: Cardiovascular Research - June 20, 2013 Category: Cardiology Authors: Hermida, N., Markl, A., Hamelet, J., Van Assche, T., Vanderper, A., Herijgers, P., van Bilsen, M., Hilfiker-Kleiner, D., Noppe, G., Beauloye, C., Horman, S., Balligand, J.-L. Tags: Cardiac biology and remodelling Source Type: research

ETC-1002 regulates immune response, leukocyte homing, and adipose tissue inflammation via LKB1-dependent activation of macrophage AMPK Research Articles
ETC-1002 is an investigational drug currently in Phase 2 development for treatment of dyslipidemia and other cardiometabolic risk factors. In dyslipidemic subjects, ETC-1002 not only reduces plasma LDL cholesterol but also significantly attenuates levels of hsCRP, a clinical biomarker of inflammation. Anti-inflammatory properties of ETC-1002 were further investigated in primary human monocyte-derived macrophages and in in vivo models of inflammation. In cells treated with ETC-1002, increased levels of AMP-activated protein kinase (AMPK) phosphorylation coincided with reduced activity of MAP kinases and decreased production...
Source: The Journal of Lipid Research - July 10, 2013 Category: Lipidology Authors: Filippov, S., Pinkosky, S. L., Lister, R. J., Pawloski, C., Hanselman, J. C., Cramer, C. T., Srivastava, R. A. K., Hurley, T. R., Bradshaw, C. D., Spahr, M. A., Newton, R. S. Tags: Research Articles Source Type: research

Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation.
Abstract Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of >50μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized L...
Source: Toxicology and Applied Pharmacology - July 8, 2013 Category: Toxicology Authors: Chen JH, Tsai CW, Wang CP, Lin HH Tags: Toxicol Appl Pharmacol Source Type: research

TRAF3IP2 mediates interleukin-18-induced cardiac fibroblast migration and differentiation.
Abstract TRAF3IP2 is a cytoplasmic adapter protein and an upstream regulator of IKK/NF-κB and JNK/AP-1. Here we demonstrate for the first time that the proinflammatory cytokine interleukin (IL)-18 induces TRAF3IP2 expression in primary cardiac fibroblasts (CF) in a Nox4/hydrogen peroxide-dependent manner. Silencing TRAF3IP2 using a phosphorothioated, 2-O'-methyl modified, cholesterol-tagged TRAF3IP2 siRNA duplex markedly attenuated IL-18-induced NF-κB and AP-1 activation and CF migration. Using co-IP/IB and co-localization experiments, we show that Nox4 physically associates with IL-18 receptor proteins, and IL-...
Source: Cellular Signalling - July 18, 2013 Category: Cytology Authors: Valente AJ, Sakamuri SS, Siddesha JM, Yoshida T, Gardner JD, Prabhu R, Siebenlist U, Chandrasekar B Tags: Cell Signal Source Type: research

Japanese encephalitis virus infects porcine kidney epithelial PK15 cells via clathrin- and cholesterol-dependent endocytosis
Conclusions: Taken together, our results demonstrate that JEV enters porcine kidney epithelial PK15 cells through cholesterol- and clathrin-mediated endocytosis.
Source: Virology Journal - August 12, 2013 Category: Virology Authors: Songbai YangMinhui HeXiangdong LiuXinyun LiBin FanShuhong Zhao Source Type: research

Role of Claudin-5 in the Attenuation of Murine Acute Lung Injury by Simvastatin.
Abstract The statins are now recognized to have pleiotropic properties including augmentation of endothelial barrier function. To explore the mechanisms involved, we investigated the effect of simvastatin on endothelial cell (EC) tight junctions. Western blotting of human pulmonary artery EC treated with simvastatin (5 µM) confirmed a significant time-dependent increase (16-48 h) in claudin-5 protein expression compared to controls without detectable alterations in ZO-1 or occludin. These effects were associated with membrane translocation of VE-cadherin while knockdown of VE-cadherin (siRNA) inhibited simvastati...
Source: American Journal of Respiratory Cell and Molecular Biology - September 12, 2013 Category: Molecular Biology Authors: Chen W, Sharma R, Rizzo AN, Siegler JH, Garica JG, Jacobson JR Tags: Am J Respir Cell Mol Biol Source Type: research

New class of drugs lowers cholesterol in first human trial
A new class of cholesterol-lowering drugs that target a recently discovered regulator of harmful cholesterol could be an alternative or complementary treatment for the 30 million people who take statins, after the first trial in humans confirms the technique's feasibility and safety. A single dose of the small interfering ribonucleic acid (siRNA) drug candidate ALN-PCS cut levels of LDL cholesterol (bad cholesterol) in healthy volunteers by up to 57%, and 40% on average more than those given a placebo, according to the new research published in The Lancet...
Source: Health News from Medical News Today - October 3, 2013 Category: Consumer Health News Tags: Cholesterol Source Type: news

Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity.
In this study we synthesized lipid unilamellar nanoparticles (NPs) that can selectively deliver Kv1.3 siRNAs into TM cells in vitro. NPs made from a mixture of phosphatidylcholine, pegylated/biotinylated phosphoethanolamine and cholesterol were functionalized with biotinylated-CD45RO (cell surface marker of TM's) antibodies via fluorophore-conjugated streptavidin (CD45RO-NPs). Incubation of T cells with CD45RO-NPs resulted into the selective attachment and endocytosis of the NPs into TM's. Furthermore, the siRNA against Kv1.3, encapsulated into the CD45RO-NPs, was released into the cytosol. Consequently, the expression of...
Source: Biomaterials - September 26, 2013 Category: Materials Science Authors: Hajdu P, Chimote AA, Thompson TH, Koo Y, Yun Y, Conforti L Tags: Biomaterials Source Type: research

Activation of mTOR modulates SREBP-2 to induce foam cell formation through increased retinoblastoma protein phosphorylation
Conclusion Our findings demonstrate for the first time that inflammation disrupts LDLr feedback regulation through the activation of the mTOR pathway. Increased mTORC1 activity was found to up-regulate SREBP-2-mediated cholesterol uptake through Rb phosphorylation.
Source: Cardiovascular Research - November 13, 2013 Category: Cardiology Authors: Ma, K. L., Liu, J., Wang, C. X., Ni, J., Zhang, Y., Wu, Y., Lv, L. L., Ruan, X. Z., Liu, B. C. Tags: Vascular biology Source Type: research