vitamin d receptor activator

Role of vitamin D in cardiovascular disease. 2hb8: Crystal structure of VDR LBD in complex with 2alpha-methyl calcitriol, 1ynw: Crystal Structure of Vitmain D Receptor and 9-cis Retinoic Acid Receptor DNA-Binding Domains Bound to a DR3 Response Element, 1kb2: Crystal Structure of VDR DNA-binding Domain Bound to Mouse Osteopontin (SPP) Response Element, 1db1: CRYSTAL STRUCTURE OF THE NUCLEAR RECEPTOR FOR VITAMIN D COMPLEXED TO VITAMIN D. 1s0z: Crystal structure of the VDR LBD complexed to seocalcitol. This receptor also functions as a receptor for the secondary bile acid lithocholic acid. Here we studied the effect of vitamin D receptor activation on serum creatinine, creatinine generation, and its clearance. Patients with good magnesium levels required less vitamin D supplementation to achieve good vitamin D levels. FOIA Bethesda, MD 20894, Copyright Genetic polymorphisms associated with reactive oxygen species and blood pressure regulation. VDR is also involved in microRNA-directed post transcriptional mechanisms. In mice lacking VDR or CYP27B1 (1Î±-hydroxylase - an enzyme, which converts vitamin D to its active form), in addition to the expected phenotype (hypocalcaemia, secondary hyperparathyroidism and osteomalacia), development of hypertension and cardiac hypertrophy were also observed. [14] These studies have revealed novel actions of the unliganded VDR in regulating the post-morphogenic hair cycle. Besides cardiac hypertrophy, cardiac fibrosis is a key element of adverse cardiac remodeling. Would you like email updates of new search results? Toxins (Basel). Title:Vitamin D and Vitamin D Receptor Activators in Treatment of Hypertension and Cardiovascular Disease VOLUME: 14 ISSUE: 1 Author(s):Agata Franczyk, Katarzyna Stolarz-Skrzypek, Anna Wesołowska and Danuta Czarnecka Affiliation:I Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, 17 Kopernika Street, 31 … Moreover, these mice presented with overexpression of renin and atrial natriuretic peptide. [6] In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13.11. Activation of the vitamin D–vitamin D receptor (VDR) axis has been shown to reduce blood pressure and left ventricular (LV) hypertrophy. 2018 Dec 6;2018:9295147. doi: 10.1155/2018/9295147. Vitamin D, vitamin D receptor and the importance of its activation in patients with chronic kidney disease Jordi Bover1, Jesús Egido2, Elvira Fernández-Giráldez3, Manuel Praga4, 2007 Apr;16(4):407-11. doi: 10.1517/13543784.16.4.407. [§ 1]. Vitamin D receptor activator and prevention of cardiovascular events in hemodialysis patients—rationale and design of the Japan Dialysis Active Vitamin D (J-DAVID) trial Tetsuo Shoji1*, Masaaki Inaba2, Yoshiki Nishizawa3 and for J-DAVID Investigators Abstract A single nucleotide polymorphism in the initiation codon results in an alternate translation start site three codons downstream. Treatment with a vitamin D receptor activator (VDRA) has survival benefits probably related to its effects beyond the traditional role in mineral metabolism. Paricalcitol (19-nor-1,25-hydroxi-vitamin [D.sub.2]), a selective, new generation vitamin D receptor activator, has been proven to be beneficial in the control of secondary hyperparathyroidism both in hemodialysis and predialysis patients with less calcemic and phosphatemic effects [16, 17]. BACKGROUND: Activation of the vitamin D-vitamin D receptor (VDR) axis has been shown to reduce blood pressure and left ventricular (LV) hypertrophy. Observational studies have shown that the use of vitamin D receptor activators (VDRAs) is associated with lower risk of death from all-cause and cardiovascular disease (CVD) in dialysis populations regardless of serum parathyroid hormone (PTH) … Are the new vitamin D receptor activators (VDRAs) more useful in the treatment of SHPT for their reduced risk of hypercalcemia and hyperphosphatemia in haemodialysis (HD) patients? Many cells that play an important role in the cardiovascular system express the Vitamin D receptor (VDR) and respond to 1,25-(OH)2D (the active product of vitamin D conversion by hydroxylase) with cell-specific function and gene regulation. eCollection 2019. Vitamin D receptor activators (VDRA) may exert pleiotropic effects on cardiovascular disease, malignancy, and infections among dialysis patients, but recent studies have mainly focused on cardiovascular outcomes. PURPOSE: The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) patients. [8] The receptor regulates a variety of other metabolic pathways, such as those involved in the immune response and cancer. The purpose of the immune system is to recognize and clear pathogens from the body. Both vitamin D receptor activator (VDRA) treatment and dietary sodium restriction potentiate the efficacy of renin–angiotensin–aldosterone-system (RAAS) blockade to reduce albuminuria. Please enable it to take advantage of the complete set of features! 2019 Dec 31;4:e298-e303. COVID-19 is an emerging, rapidly evolving situation. Tetsuo Shoji, Masaaki Inaba, Yoshiki Nishizawa, Vitamin D receptor activator and prevention of cardiovascular events in hemodialysis patients—rationale and design of the Japan Dialysis Active Vitamin D (J-DAVID) trial, Renal Replacement Therapy, 10.1186/s41100-016-0029-z, 2, 1, (2016). Without magnesium, Vitamin D is not really useful or safe,” says study co-author Mohammed S. Razzaque, MBBS, PhD, a professor of pathology at Lake Erie College of Osteopathic Medicine. Vitamin D plays an essential role in calcium homeostasis and bone metabolism, but recent research has exposed a larger spectrum of biological actions that also includes induction of cell proliferation, immunomodulation, and control of other hormonal systems. Read our disclaimer for details. studies in Vitamin D Receptor category. The main purpose of this article is to review the role of vitamin D and vitamin D receptor activators in cardiovascular diseases, especially hypertension and its treatment. Br J Pharmacol. [8] Glucocorticoids decrease VDR expression. 2019;20(10):984-995. doi: 10.2174/1389203720666190807130504. [7], VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals. Meta-Analysis of the Association Between the rs228570 Vitamin D Receptor Gene Polymorphism and Arterial Hypertension Risk. Disclaimer. Vitamin D controls T cell antigen receptor signaling and activation of human T cells Phospholipase C (PLC) isozymes are key signaling proteins downstream of many extracellular stimuli. Liang X, Chen M, Qu P, Hao G, Huang Y, Chen J, Li T. Int J Hypertens. The vitamin D receptor (VDR) is a member of the nuclear receptor/steroid hormone receptor superfamily. With good Mg levels, less vitamin D needed. Vitamin-D Receptor Activation (VDRA) in Chronic Kidney Disease (SOLID) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Recent studies in dialysis patients suggest that paricalcitol, a selective activator of the vitamin D receptor (VDR), is associated with a more favorable efficacy to side effect profile than calcitriol, with less morbidity and better survival. However, occasionally unwanted immune reactions against self-tissue that lead to autoimmune diseases occur. VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from inadequate cutaneous production and/or low dietary intake. Vitamin-D deficient patients present a higher risk of cardiovascular disease than the general population. The VDR heterodimer then enters the nucleus and binds to Vitamin D responsive elements (VDRE) in genomic DNA. Loss of VDR is associated with hair loss in experimental animals. eCollection 2018. The binding of the vitamin D3 to VDR causes conformational changes that permit VDR-RXR heterodimer formation and VDR/ SRC-1 (transcriptional co-activator proteins) interactions. Alternative splicing results in multiple transcript variants encoding the same protein. Besides cardiac hypertrophy, cardiac fibrosis is a key element of adverse cardiac remodeling. Vitamin D receptor has been shown to interact with many other factors which will affect transcription activation: Click on genes, proteins and metabolites below to link to respective articles. We discuss the possible beneficial effects of a selective activator of vitamin D receptor, paricalcitol, on the cardiovascular system in chronic heart failure patients and chronic kidney patients, in light of new trials. VDR activation induces the expression of liver and intestinal phase I detox enzymes (e.g., CYP2C9 and 3A4) that play major roles in metabolizing drugs and toxins (R). HÃ©naut L, Candellier A, Boudot C, Grissi M, Mentaverri R, Choukroun G, Brazier M, Kamel S, Massy ZA. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Basically, 1 α,25(OH)2D3 is synthesized by metabolic conversions in the liver and kidney, and can bind to the vitamin D receptor (VDR) to express biological activities through modulating transcription of target genes. A poor VDR increases the risk of 55 health problems click here for details The risk of 44 diseases at least double with poor Vitamin D Receptor as of Oct 2019 Treatment with calcitriol, the active form of vitamin D, reduces serum PTH levels but may result in both hypercalcemia and hyperphosphatemia, increasing the risk of vascular calcification in CKD. [10], Downstream targets of this nuclear hormone receptor include many genes involved in mineral metabolism. The frequency of autoimmune diseases such as type 1 diabetes mellitus (Staples et al., 2003; Sloka et al., 2010), rheumatoid arthritis (Vieira et al., 2010), multiple sclerosis (MS) (Hogancamp et al., 1997), and inflammatory bowel disease (Khalili et al., 2012) has been linked to geographic location with a higher in… 8600 Rockville Pike Unfortunately, the natural, non-selective vitamin D receptor activator (VDRA), calcitriol, is associated to higher serum calcium and phosphate levels, thus worsening CV risk in CKD. Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates, raising concerns that its use may be detrimental to kidney function. 2009 Sep;158(2):395-412. doi: 10.1111/j.1476-5381.2009.00171.x. Dowd, P.N. Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.RANKL is known as a type II membrane protein and is a member of … Unable to load your collection due to an error, Unable to load your delegates due to an error. METHODS: In this review, we describe the new VDRA, paricalcitol (1,25-dihydroxy-19-nor-vitamin D2), which suppresses PTH secretion with minimal increases on serum calcium and phosphate levels. Other forms of vitamin D bind with lower affinity, as does the secondary bile acid lithocholic acid. These cells include cardiomyocytes, vascular endothelial cells, vascular smooth muscle cells, phagocytes, and cells of the nephron, which produce renin. Privacy, Help Nakhl S, Sleilaty G, Chouery E, Salem N, Chahine R, FarÃ¨s N. Arch Med Sci Atheroscler Dis. [9], Mutations in this gene are associated with type II vitamin D-resistant rickets. VDR may play a role in regulating smooth-muscle-cell (SMC) proliferation, thrombosis, fibrinolysis and vessel relaxation. The potential for vitamin D receptor activation in cardiovascular research. Paricalcitol, a vitamin d receptor activator, inhibits tumor formation in a murine model of uterine fibroids. The vitamin D receptor plays an important role in regulating the hair cycle. Observational studies suggest that in hemodialysis patients the use of a vitamin D receptor (VDR) activator, such as calcitriol, doxercalciferol, paricalcitol, or alfacalcidol, is associated with a reduced mortality when compared with nonusers of any VDR activator. The ubiquitous distribution of vitamin D receptors in the human body is responsible for the pleiotropic effects of vitamin D-receptor activation. Shorter sunlight exposure or reduced pro-vitamin D intake causes rickets. 2ham: Crystal structure of VDR LBD complexed to 2alpha-propyl-calcitriol, 2har: Crystal structure of VDR LBD in complex with 2 alpha-(3-hydroxy-1-propoxy) calcitriol, 1kb6: Crystal Structure of VDR DNA-binding Domain Bound to Rat Osteocalcin (OC) Response Element, 1ie9: Crystal Structure Of The Nuclear Receptor For Vitamin D Ligand Binding Domain Bound to MC1288. 1s19: Crystal structure of VDR ligand binding domain complexed to calcipotriol. The influence of VDR activators on the modulation of renin expression and vascular function may reduce mortality, organ damage, and cardiovascular morbidity in VDR-activator-treated patients with hypertension. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows similarity of sequence to the steroid and thyroid hormone receptors. The receptor belongs to the family of trans-acting transcriptional regulatory factors and shows similarity of sequence to the steroid and thyroid hormone receptors. Potential for vitamin D receptor agonists in the treatment of cardiovascular disease. The VDR gene encodes the nuclear hormone receptor for vitamin D3. 2019 Sep 12;11(9):529. doi: 10.3390/toxins11090529. 2020 Sep 1;11(5):1211-1220. doi: 10.1093/advances/nmaa076. Clipboard, Search History, and several other advanced features are temporarily unavailable. Vitamin D tests cannot detect Vitamin D Receptor (VDR) problems A poor VDR restricts Vitamin D from getting in the cells It appears that 30% of the population have a poor VDR (40% of the Obese) . [5] Calcitriol (the active form of vitamin D, 1,25-(OH)2vitamin D3) binds to VDR, which then forms a heterodimer with the retinoid-X receptor. 2has: Crystal structure of VDR LBD in complex with 2alpha-(1-propoxy) calcitriol, 1ie8: Crystal Structure Of The Nuclear Receptor For Vitamin D Ligand Binding Domain Bound to KH1060, 1txi: Crystal structure of the vdr ligand binding domain complexed to TX522, 2hb7: Crystal structure of VDR LBD in complex with 2alpha(3-hydroxy-1-propyl) calcitriol, 1kb4: Crystal Structure of VDR DNA-binding Domain Bound to a Canonical Direct Repeat with Three Base Pair Spacer (DR3) Response Element, Transcription factor activated by vitamin D. The interactive pathway map can be edited at WikiPathways: GO:0038050, GO:0004886, GO:0038051 nuclear receptor activity, GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity, GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific, transcription regulatory region sequence-specific DNA binding, RNA polymerase II regulatory region sequence-specific DNA binding, ligand-dependent nuclear receptor transcription coactivator activity, RNA polymerase II transcription factor complex, negative regulation of cell proliferation, positive regulation of apoptotic process involved in mammary gland involution, positive regulation of keratinocyte differentiation, regulation of calcidiol 1-monooxygenase activity, steroid hormone mediated signaling pathway, regulation of transcription, DNA-templated, positive regulation of transcription from RNA polymerase II promoter, negative regulation of keratinocyte proliferation, negative regulation of transcription from RNA polymerase II promoter, negative regulation of transcription, DNA-templated, transcription initiation from RNA polymerase II promoter, positive regulation of vitamin D 24-hydroxylase activity, mammary gland branching involved in pregnancy, GRCh38: Ensembl release 89: ENSG00000111424, GRCm38: Ensembl release 89: ENSMUSG00000022479, "Vitamin D activation of functionally distinct regulatory miRNAs in primary human osteoblasts", "Molecular Mechanisms for Regulation of Intestinal Calcium Absorption by Vitamin D and Other Factors", "Entrez Gene: VDR vitamin D (1,25- dihydroxyvitamin D3) receptor", "The Vitamin D Receptor Is Required for Activation of cWnt and Hedgehog Signaling in Keratinocytes", "BAG1L enhances trans-activation function of the vitamin D receptor", "The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome", "Membrane Localization, Caveolin-3 Association and Rapid Actions of Vitamin D Receptor in Cardiac Myocytes", "Antagonistic action of a 25-carboxylic ester analogue of 1alpha, 25-dihydroxyvitamin D3 is mediated by a lack of ligand-induced vitamin D receptor interaction with coactivators", "Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription", "Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs", "Isolation and characterization of a novel coactivator protein, NCoA-62, involved in vitamin D-mediated transcription", "Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription", "Genetics and biology of vitamin D receptor polymorphisms", "Minireview: vitamin D receptor: new assignments for an already busy receptor", "RXR alpha, a promiscuous partner of retinoic acid and thyroid hormone receptors", "A unique mutation in the vitamin D receptor gene in three Japanese patients with vitamin D-dependent rickets type II: utility of single-strand conformation polymorphism analysis for heterozygous carrier detection", "The molecular basis of hereditary 1,25-dihydroxyvitamin D3 resistant rickets in seven related families", "A unique point mutation in the human vitamin D receptor chromosomal gene confers hereditary resistance to 1,25-dihydroxyvitamin D3", "Cloning and expression of full-length cDNA encoding human vitamin D receptor", "Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3", "Human vitamin D receptor phosphorylation by casein kinase II at Ser-208 potentiates transcriptional activation", Vitamin D Receptor: Molecule of the Month, United States National Library of Medicine, transcription factor/coregulator deficiencies, https://en.wikipedia.org/w/index.php?title=Vitamin_D_receptor&oldid=1011048899, Short description is different from Wikidata, Wikipedia articles incorporating text from the United States National Library of Medicine, Creative Commons Attribution-ShareAlike License, Overview of all the structural information available in the, This page was last edited on 8 March 2021, at 19:06. Since clinical use of calcitriol is largely limited, because of the side effect of hypercalcemia, calcitriol analogues have been synthesized to obtain compounds with better therapeutic profiles. Expert Opin Investig Drugs. Due to the high prevalence of hypovitaminosis D among patients with high cardiovascular risk, vitamin D supplementation therapy may be warranted in this population. Nunes IFOC, Cavalcante AACM, Alencar MVOB, Carvalho MDF, Sarmento JLR, Teixeira NSCCA, Paiva AA, Carvalho LR, Nascimento LFM, Cruz MSP, Rogero MM, Lima ACB, Carvalho CMRG. Vitamin D and Vitamin D Receptor: New Insights in the Treatment of Hypertension. [11] VDR gene variants seem to influence many biological endpoints, including those related to osteoporosis [12]. Activation of vitamin D is severely impaired in patients with advanced stages of chronic kidney disease, particularly those on hemodialysis. We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. Recent data suggest an emerging role for the vitamin D receptor activator (VDRA) paricalcitol in the treatment of SHPT. Epub 2009 Apr 9. VDR activators (calcitriol and paricalcitol) are available for the treatment of vitamin D deficiency, which can result from inadequate cutaneous production and/or low dietary intake. D.R. We hypothesized that VDRA reduces oxidative stress in hemodialysis (HD) patients. National Library of Medicine Compelling results have arisen from previous studies of mice with disrupted genes of the vitamin D signaling pathways. 1DB1, 1IE8, 1IE9, 1KB2, 1KB4, 1KB6, 1S0Z, 1S19, 1TXI, 1YNW, 2HAM, 2HAR, 2HAS, 2HB7, 2HB8, 3A2I, 3A2J, 3A3Z, 3A40, 3A78, 3AUQ, 3AUR, 3AX8, 3AZ1, 3AZ2, 3AZ3, 3B0T, 3CS4, 3CS6, 3KPZ, 3M7R, 3OGT, 3P8X, 3TKC, 3VHW, 4G2I, 3W0A, 3W0C, 3W0Y, 3WGP, 3WWR, 4ITE, 4ITF, 4PA2, 3X31, 3X36, The vitamin D receptor (VDR also known as the calcitriol receptor) is a member of the nuclear receptor family of transcription factors. All content on this website, including dictionary, thesaurus, literature, geography, and other reference data is for informational purposes only. Cardiovascular disease in chronic kidney failure: the role of VDR activators. [17]. This article incorporates text from the United States National Library of Medicine, which is in the public domain. Among 8,675 patients who started dialysis in … MacDonald, in Encyclopedia of Biological Chemistry (Second Edition), 2013 Abstract. New Insights into the Roles of Monocytes/Macrophages in Cardiovascular Calcification Associated with Chronic Kidney Disease. 2006 Mar;7(3):206-13. Recent data showed that the selective VDRA paricalcitol might have ameliorative CV effects. Adv Nutr. [9], The VDR gene encodes the nuclear hormone receptor for vitamin D. The most potent natural agonist is calcitriol (1,25-dihydroxycholecalciferol) and the vitamin D2 homologue ercalcitriol, 1-alpha,25-dihydroergocalciferol) is also a strong activator. These receptors function as ligand-activated, transcriptional regulatory proteins. Recent clinical observations have shown that VDR activator therapy provides survival benefit and also has a positive impact on cardiovascular function. Wu-Wong JR, Tian J, Nakane M, Ma J, Fey TA, Kroeger P, Fryer RM, Reinhart GA. Curr Opin Investig Drugs. [8] Many types of immune cells also express VDR. Vitamin D receptor activators (VDRAs) are used to treat SHPT, but the comparative efficacy and safety between paricalcitol and other vitamin D receptor activators for management of SHPT in dialysis patients has been unproven. Accessibility Curr Protein Pept Sci. According to recent reports, vitamin D receptor activators (VDRAs) play an important role in the prevention of premature vascular aging (Marangella et al., 2009, Franczyk et al., 2014). 2019 Aug;19(4):315-336. doi: 10.1038/s41397-019-0082-4. Prevention and treatment information (HHS). doi: 10.5114/amsad.2019.91437. Role of vitamin D receptor activators on cardiovascular risk Jose M. Valdivielso1 and Juan C. Ayus2 1Laboratorio de Nefrologı´a Experimental, Hospital Universitario Arnau de Vilanova, IRBLLEIDA, Lleida, Spain and 2Renal Consultants of Houston, Houston, Texas, USA Cardiovascular complications are the main cause of death in Pharmacogenomics J. Researchers have focused their efforts in elucidating the role of VDR polymorphisms in different diseases and normal phenotypes such as the HIV-1 infection susceptibility and progression or the natural aging process. This site needs JavaScript to work properly. VDR binding results in expression or transrepression of many specific gene products. Vitamin-D deficient patients present a higher risk of cardiovascular disease than the general population. Careers. The most remarkable findings include the report of VDR variants that bolster vitamin-D action and that are directly correlated with AIDS progression rates, that VDR association with progression to AIDS follows an additive model [15] and the role of FokI polymorphism as a risk factor for enveloped virus infection as revealed in a meta-analysis. The Association of Vitamin A and Vitamin D with Hypertension in Children: A Case-Control Study. Vitamin D is most essential secosteroid produced its systemic functions via complex with steroid/thyroid nuclear receptor called vitamin D receptor (VDR). Epub 2019 Feb 6. [13] Experimental studies have shown that the unliganded VDR interacts with regulatory regions in cWnt (wnt signaling pathway) and sonic hedgehog target genes and is required for the induction of these pathways during the postnatal hair cycle. The Vitamin D Receptor is important for hair growth and loss of VDR is associated with hair loss in experimental animals (R). [16] The importance of this gene has also been noted in the natural aging process were 3’UTR haplotypes of the gene showed an association with longevity.