Protective actions of vitamin D, anandamide and melatonin during vascular inflammation: Epigenetic mechanisms involved

Abstract Funding Acknowledgements Type of funding sources: None. Aim To investigate the role of markers of vascular inflammation, vitamin D, parathyroid hormone as predictors of increased pulse-wave velocity (PWV) and degenerative bone changes in postmenopausal women with arterial hypertension (AH). Methods 164 females were examined. Gr.1 included 42 healthy individuals, Gr.2 - 58 patients with AH and Gr.3 - 64 postmenopausal women with AH and osteoporosis. Parameters of blood pressure monitoring; PWV, osteodensitometry (T-Score); inflammatory markers: hsCRP, TNFα, homocysteine, IL-1β, 6, 8, endothelin-1; lipid profile parameters; sex and parathyroid hormones, vitamin D were measured. Results In Gr.3 excess levels of PWV, hsCRP, homocysteine, IL8, total cholesterol, LDL cholesterol, endothelin-1 and parathyroid hormone was detected with decrease in the level of sex hormones and vitamin D. Besides, negative correlations of T-Score with age, PWV, duration of menopause, IL-6, hsCRP were registered; positive correlations between PWV with IL6, LDL cholesterol, hsCRP, endothelin-1, DBP variability were found. The logistic regression method revealed the main markers that affect increase of PWV, such as hsCRP and endothelin-1.Rise of each marker by unit of measurement leads to increase in PWV by 1.3 times and 2.4%, respectively. In Gr.2 increase in PWV level of more than 12.05 m/s was associated with 3.8-fold increase in the risk of osteoporosis. In Gr.3 increase in PWV level on 1 m/s was associated with 6 fold increase in the risk of osteoporosis. Conclusions Elevated levels of PWV are associated with markers of inflammation, levels of parathyroid hormone, vitamin D, T-Score and may be part of the pathogenesis of the cardiovascular continuum in postmenopausal women, which will require an individual approach to the treatment of AH with comorbid metabolic disorders.

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Extrarenal Vitamin D Hydroxylase Expression and Activity in Normal and Malignant Cells: Modification of Expression by Epigenetic Mechanisms and Dietary Substances

Nutrition Reviews ◽

10.1111/j.1753-4887.2007.tb00334.x ◽

2008 ◽

Vol 65 ◽

pp. S108-S112 ◽

Cited By ~ 1

Author(s):

Heide S. Cross

Keyword(s):

Vitamin D ◽

Epigenetic Mechanisms ◽

Malignant Cells ◽

Expression And Activity

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Role of Vitamin D in Cardiometabolic Diseases

Journal of Diabetes Research ◽

10.1155/2013/243934 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 15

Author(s):

Chaoxun Wang

Keyword(s):

Metabolic Syndrome ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Vascular Inflammation ◽

Left Ventricular ◽

Bone Diseases ◽

The Body ◽

Cvd Risk ◽

Increased Risk ◽

Vitamin D Levels

Vitamin D deficiency is a highly prevalent condition. Low vitamin D levels have long been associated with bone diseases, such as rickets in children and osteomalacia and osteoporosis in adults. However, it has become apparent in recent years that adequate vitamin D levels are also important for optimal functioning of many organs and tissues throughout the body, including the cardiovascular system. Evolving data indicate that vitamin D deficiency is associated with an increased risk of cardiovascular disease (CVD). Studies have shown that low vitamin D levels are associated with hypertension, diabetes, metabolic syndrome, left ventricular hypertrophy, and chronic vascular inflammation, all of which are risk factors for CVD. This paper reviews the definition and pathophysiology of vitamin D deficiency, clinical evidence linking vitamin D and CVD risk, diabetes and its complications, and metabolic syndrome.

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New Molecules Modulating Bone Metabolism – New Perspectives in the Treatment of Osteoporosis

Physiological Research ◽

10.33549/physiolres.933720 ◽

2017 ◽

pp. S341-S347 ◽

Cited By ~ 3

Author(s):

I. ZOFKOVA ◽

J. BLAHOS

Keyword(s):

Vitamin D ◽

Osteoblast Differentiation ◽

Bone Microstructure ◽

Bmp Signaling ◽

Vitamin D Metabolites ◽

Anabolic Effect ◽

Epigenetic Mechanisms ◽

Direct Effects ◽

Treatment Of Osteoporosis ◽

Osteoblast Activity

In this review the authors outline traditional antiresorptive pharmaceuticals, such as bisphosphonates, monoclonal antibodies against RANKL, SERMs, as well as a drug with an anabolic effect on the skeleton, parathormone. However, there is also a focus on non-traditional strategies used in therapy for osteolytic diseases. The newest antiosteoporotic pharmaceuticals increase osteoblast differentiation via BMP signaling (harmine), or stimulate osteogenic differentiation of mesenchymal stem cells through Wnt/β-catenin (icarrin, isoflavonoid caviunin, or sulfasalazine). A certain promise in the treatment of osteoporosis is shown by molecules targeting non-coding microRNAs (which are critical for osteoclastogenesis) or those stimulating osteoblast activity via epigenetic mechanisms. Vitamin D metabolites have specific antiosteoporotic potencies, modulating the skeleton not only via mineralization, but markedly also through the direct effects on the bone microstructure.

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The world pandemic of vitamin D deficiency could possibly be explained by cellular inflammatory response activity induced by the renin-angiotensin system

AJP Cell Physiology ◽

10.1152/ajpcell.00403.2011 ◽

2013 ◽

Vol 304 (11) ◽

pp. C1027-C1039 ◽

Cited By ~ 65

Author(s):

Marcelo Ferder ◽

Felipe Inserra ◽

Walter Manucha ◽

León Ferder

Keyword(s):

Vitamin D ◽

Vascular Inflammation ◽

Renin Angiotensin System ◽

Left Ventricular ◽

Point Of View ◽

The Other ◽

Angiotensin System ◽

Renin Angiotensin ◽

Immunological Mechanisms ◽

Cellular Inflammatory Response

This review attempts to show that there may be a relationship between inflammatory processes induced by chronic overstimulation of the renin-angiotensin system (RAS) and the worldwide deficiency of vitamin D (VitD) and that both disorders are probably associated with environmental factors. Low VitD levels represent a risk factor for several apparently different diseases, such as infectious, autoimmune, neurodegenerative, and cardiovascular diseases, as well as diabetes, osteoporosis, and cancer. Moreover, VitD insufficiency seems to predispose to hypertension, metabolic syndrome, left ventricular hypertrophy, heart failure, and chronic vascular inflammation. On the other hand, inappropriate stimulation of the RAS has also been associated with the pathogenesis of hypertension, heart attack, stroke, and hypertrophy of the left ventricle and vascular smooth muscle cells. Because VitD receptors (VDRs) and RAS receptors are almost distributed in the same tissues, a possible link between VitD and the RAS is even more plausible. Furthermore, from an evolutionary point of view, both systems were developed simultaneously, actively participating in the regulation of inflammatory and immunological mechanisms. Changes in RAS activity and activation of the VDR seem to be inversely related; thus any changes in one of these systems would have a completely opposite effect on the other, making it possible to speculate that the two systems could have a feedback relationship. In fact, the pandemic of VitD deficiency could be the other face of increased RAS activity, which probably causes lower activity or lower levels of VitD. Finally, from a therapeutic point of view, the combination of RAS blockade and VDR stimulation appears to be more effective than either RAS blockade or VDR stimulation individually.

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Postmenopausal Calcium and Vitamin D Supplements Controversy: Do They Increase Cardiovascular Risk?

Revista de Chimie ◽

10.37358/rc.18.4.6236 ◽

2018 ◽

Vol 69 (4) ◽

pp. 956-960

Author(s):

Serban Balanescu ◽

Violeta Claudia Bojinca ◽

Adrian Iancu ◽

Mihai Bojinca ◽

Andra Balanescu

Keyword(s):

Vitamin D ◽

Cardiovascular Risk ◽

Vascular Calcification ◽

Serum Calcium ◽

Calcium Intake ◽

Vascular Inflammation ◽

Cardiovascular Outcome ◽

Ectopic Tissue ◽

Coronary Events ◽

Atherosclerotic Process

Calcium and vitamin D are prescribed in women with osteopenia-osteoporosis to prevent fractures. These bone events increase morbidity and mortality justifying therapy to prevent bone loss. These elderly patients also have cardiovascular risk factors, atherosclerosis and vascular calcifications. Multiple trials demonstrated a relationship between the latter, coronary events and cardiovascular mortality. In these patients, ectopic tissue mineralization may worsen cardiovascular outcome. Calcium intake correlates neither with serum calcium, vascular calcification nor cardiovascular events. However serum calcium-phosphate product is related to vascular calcification and outcome. The main cause for vascular calcification is systemic inflammation and local atherosclerotic process with specific interactions between macrophages and smooth muscle cells. This review examines calcium intake, serum calcium concentration, systemic and vascular inflammation, the mechanisms of vascular calcification and their impact on cardiovascular outcome.

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Dysregulation of Metabolic Genes May Be Normalized by Epigenetic Drugs (Vorinostat, Decitabine) and Nutritional Compounds (Genistein, Vitamin D) in Leukemic Cells.

Blood ◽

10.1182/blood.v114.22.4423.4423 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4423-4423

Author(s):

Heidrun Karlic ◽

Franz Varga ◽

Elisabeth Pittermann ◽

Michael Pfeilstocker

Keyword(s):

Gene Expression ◽

Vitamin D ◽

Cell Line ◽

Vitamin D3 ◽

Large Scale ◽

Leukemic Cells ◽

Epigenetic Mechanisms ◽

Metabolic Genes ◽

Nutritional Compounds ◽

Kg1 Cells

Abstract Abstract 4423 Background Dysregulation of energy metabolism is a key feature of malignancy and known to be regulated by epigenetic mechanisms. This study explores gene expression in the KG1 cell line and a primary culture of leukemic blasts from a patient, both incubated with SAHA (suberoyl anilide hydroxamic acid, also known as Vorinostat) in comparison to other epigenetic drugs such as Decitabine (DAC) but also nutritional compounds such as genistein and vitamin D3 with a known activity on metabolism where epigenetic mechanisms play a role. Methods Following a 3 days incubation with pharmacologic concentrations of the above mentioned compounds, gene expression patterns of the KG1 cell-line were analysed on an Affymetrix Gene Expression Array and specifically evaluated by quantitative real time PCR from KG1 cells and primary leukemic cells of a patient with an AML-M2 which were cultured at the same conditions as the KG1 cells. In order to confirm epigenetic mechanisms induced by targeted drugs, methylation patterns of selected tumor suppressor genes were analyzed using specific primers for bisulfite-treated DNA. Results Our experiments show that expression of a large scale of micro RNAs which are known to be responsible for alternative splicing is stimulated by SAHA as well as DAC and to a lesser extent also Vitamin D3 and genistein, but downregulation of mitochondrial RNAs as a consequence of apoptosis was exclusively observable by SAHA. HDAC-inhibition results in clear repression of metabolic genes involved in glycolysis (5/6 genes) as well as cholesterol-biosynthesis (14/15 genes) and fatty acid synthesis (all 4 genes) which are also known to be regulated by nutrition. Classic tumour suppressor genes, transcription factors and cell-cycle regulators such as P53, P15, P16 and P21 and FOXO were (re-) activated with this treatment while MYC was down-regulated. Discussion A downregulation and thus normalization of a large scale of genes including key genes from malignancy-associated stimulation of glycolysis as well as biosynthesis of cholesterol and fatty acids was observed with SAHA and nutritional compounds such as Vitamin D and genistein. We propose that these interactions should be carefully considered in clinical application, and a combination of synergistic drugs and/or dietary strategies may provide a major advantage in future drug development. Acknowledgment Supported by Jubilaeumsfonds der Oesterreichischen Nationalbank. Disclosures: No relevant conflicts of interest to declare.

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