RESUMEN
INTRODUCTION: Vitamin D has potential benefits for extraskeletal health. These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction. We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function (EF), possibly through the abrogation of systemic inflammation. METHODS AND ANALYSIS: We will conduct a systematic review of all randomised controlled trials on vitamin D supplementation and EF lasting 12 weeks or more. The search will cover the period 2000-2015 and include studies that describe direct measures of EF, markers of endothelial cell (EC) activation and if concurrently reported, indicators of systemic inflammation. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis. If sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges' g score, for both fixed and random effect models. I(2) statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources. Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger's test. Meta-regression analysis (if feasible) will be conducted with restricted maximum likelihood (REML) estimation method, controlling for potential confounders (demographics, study methods, location, etc). A backward elimination process will be applied in the regression modelling procedure. Subgroup analysis, conditional on number of studies retrieved and their sample size, will be stratified on participant disease category, total dose administered, degree of 25(OH)D change and type of supplement used. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the popular press. TRIAL REGISTRATION NUMBER: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42014013523.
Asunto(s)
Suplementos Dietéticos , Endotelio Vascular/efectos de los fármacos , Vitamina D/farmacología , Vitaminas/farmacología , Endotelio Vascular/patología , Humanos , Inflamación/prevención & control , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Vitamina D/uso terapéutico , Vitaminas/uso terapéuticoRESUMEN
Angiogenesis is fundamental to normal placental development and aberrant angiogenesis contributes substantially to placental pathologies. The complex process of angiogenesis is regulated by transcription factors leading to the formation of endothelial cells that line the microvasculature. Homeobox genes are important transcription factors that regulate vascular development in embryonic and adult tissues. We have recently shown that placental homeobox genes HLX, DLX3, DLX4, MSX2 and GAX are expressed in placental endothelial cells. Hence, the novel homeobox genes TLX1, TLX2, TGIF, HEX, PHOX1, MEIS2, HOXB7, and LIM6 were detected that have not been reported in endothelial cells previously. Importantly, these homeobox genes have not been previously reported in placental endothelial cells and, with the exception of HEX, PHOX1 and HOXB7, have not been described in any other endothelial cell type. Reverse transcriptase PCR was performed on cDNA from freshly isolated placental microvascular endothelial cells (PLEC), and the human placental microvascular endothelial cell line HPEC. cDNAs prepared from control term placentae, human microvascular endothelial cells (HMVEC) and human umbilical vein macrovascular endothelial cells (HUVEC) were used as controls. PCR analyses showed that all novel homeobox genes tested were expressed by all endothelial cells types. Furthermore, real-time PCR analyses revealed that homeobox genes TLX1, TLX2 and PHOX1 relative mRNA expression levels were significantly decreased in HUVEC compared with microvascular endothelial cells, while the relative mRNA expression levels of MEIS2 and TGIF were significantly increased in macrovascular cells compared with microvascular endothelial cells. Thus we have identified novel homeobox genes in microvascular endothelial cells and have shown that homeobox genes are differentially expressed between micro- and macrovascular endothelial cells.