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Vitamin D AND RAS

Sabine Baumgartner, Rouyanne T Ras, Elke A Trautwein, Ronald P Mensink, Jogchum Plat
PURPOSE: Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. METHODS: Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (β-carotene, α-carotene, lycopene, lutein, zeaxanthin and β-cryptoxanthin) using a random effects model...
September 3, 2016: European Journal of Nutrition
Francesca Uberti, Vera Morsanuto, Debora Lattuada, Barbara Colciaghi, Andrea Cochis, Alessandro Bulfoni, Paola Colombo, Giorgio Bolis, Claudio Molinari
BACKGROUND: Recently, vitamin D3 (1alpha, 25-dihydroxyvitamin D) has shown its capability to take part in many extraskeletal functions and its serum levels have been related to patient survival rate and malignancy of many types of neoplasms, including ovarian cancers. Catalytic iron is a free circulating form of iron that is able to generate reactive oxygen species and consequently to promote a number of cellular and tissutal dysfunctions including tumorigenesis. In fertile women an important source of catalytic iron is derived from retrograde menstruation...
2016: Journal of Ovarian Research
Maria Vanessa Perez-Gomez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Binbin Zheng, Catalina Martín-Cleary, Marta Ruiz-Ortega, Alberto Ortiz, Beatriz Fernandez-Fernandez
INTRODUCTION: The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials. AREAS COVERED: The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action...
September 2016: Expert Opinion on Investigational Drugs
Xuanzhu Zhou, Wei Zheng, G A Nagana Gowda, Daniel Raftery, Shawn S Donkin, Brian Bequette, Dorothy Teegarden
Breast cancer is the second most common cancer among women in the US. The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D), is proposed to inhibit cellular processes and to prevent breast cancer. The current studies investigated the effect of 1,25(OH)2D on glutamine metabolism during cancer progression employing Harvey-ras oncogene transformed MCF10A human breast epithelial cells (MCF10A-ras). Treatment with 1,25(OH)2D significantly reduced intracellular glutamine and glutamate levels measured by nuclear magnetic resonance (NMR) by 23±2% each...
October 2016: Journal of Steroid Biochemistry and Molecular Biology
S Graziano, R Johnston, O Deng, J Zhang, S Gonzalo
Oncogenic Ras expression is associated with activation of the DNA damage response (DDR) pathway, as evidenced by elevated DNA damage, primarily DNA double-strand breaks (DSBs), and activation of DNA damage checkpoints, which in primary human cells leads to entry into senescence. DDR activation is viewed as a physiological barrier against uncontrolled proliferation in oncogenic Ras-expressing cells, and arises in response to genotoxic stress due to the production of reactive oxygen species that damage DNA and to hyper-replication stress...
April 4, 2016: Oncogene
X Deng, J Cheng, M Shen
BACKGROUND: It is well established that the activation of the renin-angiotensin system (RAS) and the oxidative stress caused by hyperglycemia are major mediators of the development and progression of diabetic nephropathy (DN). Vitamin D may be important in maintaining podocyte health, preventing epithelial-to-mesenchymal transformation, and suppressing renin gene expression and inflammation, but its mechanism requires clarification. This study evaluated the specific mechanism of vitamin D to DN improvement...
June 2016: Journal of Endocrinological Investigation
Hideki Fujii, Kentaro Nakai, Yuriko Yonekura, Keiji Kono, Shunsuke Goto, Michinori Hirata, Masami Shinohara, Shinichi Nishi, Masafumi Fukagawa
PURPOSE: Recent reports showed a significant association between vitamin D levels and cardiovascular disease events and mortality. In the current study, we investigated the effect of the vitamin D receptor activator maxacalcitol (OCT) on cardiac damage in a rat model of type 2 diabetes. METHODS: At 20 weeks of age, the rats were divided into three groups: vehicle-treated (DM), insulin-treated (INS) and OCT-treated (OCT). At 30 weeks, the rats were sacrificed and urinary and blood biochemical analyses and cardiac histological and immunohistochemical analyses were performed...
December 2015: Cardiovascular Drugs and Therapy
Kazim Husain, Wilfredo Hernandez, Rais A Ansari, Leon Ferder
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome...
August 26, 2015: World Journal of Biological Chemistry
Claudia Yuste, Borja Quiroga, Soledad García de Vinuesa, Maria Angeles Goicoechea, Daniel Barraca, Ursula Verdalles, Jose Luño
BACKGROUND: Vitamin D deficiency and polypharmacy is a common problem over chronic kidney disease (CKD) population. OBJECTIVES: To assess the clinical and analytical characteristics of CKD patients with 25-OH-D3 deficiency (<15 ng/mL), including the possible role of associated drugs. METHODS: A single center observational review of 137 incident patients referred to our outpatient clinic with different stages of CKD and 25-OH-D3<15ng/mL (male gender 53...
2015: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Nirupama Chandel, Kameshwar S Ayasolla, Xiqian Lan, Maria Sultana-Syed, Amrita Chawla, Rivka Lederman, Vasupradha Vethantham, Moin A Saleem, Praveen N Chander, Ashwani Malhotra, Pravin C Singhal
HIV (human immunodeficiency virus) has been reported to induce podocyte injury through down regulation of vitamin D receptor (VDR) and activation of renin angiotensin system; however, the involved mechanism is not clear. Since HIV has been reported to modulate gene expression via epigenetic phenomena, we asked whether epigenetic factors contribute to down regulation of VDR. Kidney cells in HIV transgenic mice and HIV-infected podocytes (HIV/HPs) displayed enhanced expression of SNAIL, a repressor of VDR. To elucidate the mechanism, we studied the effect of HIV on expression of molecules involved in SNAIL repressor complex formation and demonstrated that HIV enhances expression of the histone deacetylase HDAC1 and DNA methyl transferases DNMT3b and DNMT1...
October 9, 2015: Journal of Molecular Biology
Domenico Santoro, Daniela Caccamo, Silvia Lucisano, Michele Buemi, Katerina Sebekova, Daniel Teta, Luca De Nicola
For many years deficiency of vitamin D was merely identified and assimilated to the presence of bone rickets. It is now clear that suboptimal vitamin D status may be correlated with several disorders and that the expression of 1-α-hydroxylase in tissues other than the kidney is widespread and of clinical relevance. Recently, evidence has been collected to suggest that, beyond the traditional involvement in mineral metabolism, vitamin D may interact with other kidney hormones such as renin and erythropoietin...
2015: BioMed Research International
Heidrun Karlic, Roman Thaler, Christopher Gerner, Thomas Grunt, Katharina Proestling, Florian Haider, Franz Varga
The mevalonate pathway provides metabolites for post-translational modifications such as farnesylation, which are critical for the activity of RAS downstream signaling. Subsequently occurring regulatory processes can induce an aberrant stimulation of DNA methyltransferase (DNMT1) as well as changes in histone deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the mevalonate pathway are increasingly recognized as anticancer drugs. Extensive evidence indicates an intense cross-talk between signaling pathways, which affect growth, differentiation, and apoptosis either directly or indirectly via epigenetic mechanisms...
May 2015: Cancer Genetics
Elena M V de Cavanagh, Felipe Inserra, León Ferder
Caloric restriction (CR), renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation...
July 1, 2015: American Journal of Physiology. Heart and Circulatory Physiology
Patricia A Cassano, Kristin A Guertin, Alan R Kristal, Kathryn E Ritchie, Monica L Bertoia, Kathryn B Arnold, John J Crowley, JoAnn Hartline, Phyllis J Goodman, Catherine M Tangen, Lori M Minasian, Scott M Lippman, Eric Klein
BACKGROUND: The intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers. METHODS: The Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial...
2015: Respiratory Research
Ozgur Ulas Ozcan, Adalet Gurlek, Eren Gursoy, Demet Menekse Gerede, Cetin Erol
Vitamin D deficiency is associated with various cardiovascular disorders including hypertension, coronary artery disease, and heart failure. The renin-angiotensin-aldosterone system (RAS) axis is activated in vitamin D deficiency. The RAS axis also plays a role in the pathophysiology of atrial fibrillation (AF). We aimed to investigate whether vitamin D deficiency is a risk factor for the development of new-onset AF in hypertension. A total of 227 hypertensive patients were enrolled, of whom 137 had new-onset AF; 90 patients without AF were included in the control group...
April 2015: Journal of the American Society of Hypertension: JASH
Katrina M Simmons, Sarah G Beaudin, Carmen J Narvaez, JoEllen Welsh
To elucidate potential mediators of vitamin D receptor (VDR) action in breast cancer, we profiled the genomic effects of its ligand 1,25-dihydroxyvitamin D3 (1,25D) in cells derived from normal mammary tissue and breast cancer. In non-transformed hTERT-HME cells, 483 1,25D responsive entities in 42 pathways were identified, whereas in MCF7 breast cancer cells, 249 1,25D responsive entities in 31 pathways were identified. Only 21 annotated genes were commonly altered by 1,25D in both MCF7 and hTERT-HME cells...
August 2015: Journal of Cellular Biochemistry
Wei Zhang, Lulu Chen, Luqing Zhang, Ming Xiao, Jiong Ding, David Goltzman, Dengshun Miao
Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks...
February 19, 2015: Neuroscience Letters
Partab Rai, Tejinder Singh, Rivka Lederman, Amrita Chawla, Dileep Kumar, Kang Cheng, Gautam Valecha, Peter W Mathieson, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26+STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26+STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26+STZ displayed elevated (P<0.05) blood urea nitrogen (BUN) levels (P<0...
March 2015: Cellular Signalling
Walter Manucha, Bob Ritchie, León Ferder
Mitochondria are the primary generators of cellular reactive oxygen species (ROS); their pathophysiological roles in hypertension and insulin resistance are but imperfectly understood. Mitochondrial dysfunction has been linked to the etiologies of many complex diseases, but many other factors, including the upregulation of the renin-angiotensin system (RAS) and vitamin D deficiency, have also been implicated in hypertension pathogenesis. Hypertension resulting from the disruption of the RAS contributes to the risk of cardiovascular disease...
January 2015: Current Hypertension Reports
Urszula Dougherty, Reba Mustafi, Farhana Sadiq, Anas Almoghrabi, Devkumar Mustafi, Maggi Kreisheh, Sumana Sundaramurthy, Weicheng Liu, Vani J Konda, Joel Pekow, Sharad Khare, John Hart, Loren Joseph, Alice Wyrwicz, Gregory S Karczmar, Yan Chun Li, Marc Bissonnette
PURPOSE: We previously showed that EGF receptor (EGFR) promotes tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) model, whereas vitamin D suppresses tumorigenesis. EGFR-vitamin D receptor (VDR) interactions, however, are incompletely understood. Vitamin D inhibits the renin-angiotensin system (RAS), whereas RAS can activate EGFR. We aimed to elucidate EGFR-VDR cross-talk in colorectal carcinogenesis. EXPERIMENTAL DESIGN: To examine VDR-RAS interactions, we treated Vdr(+/+) and Vdr(-/-) mice with AOM/DSS...
November 15, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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