Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study

Oostrom, Olivia van; Kleijn, Dominique P.V. de; Fledderus, Joost O.; Pescatori, Mario; Stubbs, Andrew; Tuinenburg, A.; Lim, Sai Kiang; Verhaar, Marianne C.

doi:10.1186/1475-2840-8-47

Cited by 39 publications

(25 citation statements)

References 65 publications

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“…Therefore, we suggested that focused efforts should be invested to ensure that the dose of FA falls within the pharmacological range, especially in case of diabetic pregnancy (Capel and Corcoy, 2007). This result is inconsistent with that of the original study, which suggested that the gene expression profiles of EPCs from healthy controls and T1DM patients after FA treatment were very similar and that pairwise comparison showed no DEGs at an FDR of 0.05 (van Oostrom et al, 2009). We hypothesized that these differences may be due to the different method used for the analysis of microarray data.…”

Section: Discussioncontrasting

confidence: 56%

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Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus

Fang¹,

He²,

Li³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range.

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Section: Discussioncontrasting

confidence: 56%

“…This dataset was deposited by Oostrom (van Oostrom et al, 2009). EPC samples were collected from 20 patients with T1DM and 20 age-and gender-matched healthy control subjects.…”

Section: Microarray Datamentioning

confidence: 99%

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus

Fang¹,

He²,

Li³

et al. 2014

Genet. Mol. Res.

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“…Moreover, folic acid supplementation modulates EPCs transcriptome in diabetic subjects [43] . Fish oil intake, in a different study, revealed no significant effect on vascular health [44] , while a recent research showed beneficial actions a of fish-oil supplementation on cellular markers of endothelial function: increased numbers of EPCs and reduced numbers of EMPs (endothelial microparticles), thus favoring the maintenance of endothelial integrity [45] .…”

Section: Endothelial Health Maintenance: the Nutraceutical Approachmentioning

confidence: 99%

Nutraceuticals and cardiovascular risk: potential role of EPCs modulation

Russo

Lucchesi

Longo

et al. 2015

Stem Cell Transl Investig

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According to WHO cardiovascular diseases (CVDs) are the first cause of death in the world: more people die annually from CVDs than from any other cause. Vascular endothelium plays a pivotal role in the onset and progression of these pathologies and cardiovascular risk factors are frequently associated to the levels of endothelial progenitor cells (EPCs), bone marrow-derived circulating progenitors for the endothelial lineage. Since EPCs not only preserve vascular endothelium homeostasis, but might directly participate to re-endothelization and neovascularization, these cells represent an emerging protagonist in vascular competency and as such a cell model of great interest. An unhealthy diet is one of the main cardiovascular risk factor, while there is a great interest in the potential protective effects of "nutraceuticals", food-derived compounds that exert beneficial effects on human and animal health. The characterization of the endothelial effects of different nutraceuticals may provide fresh insights into their potential role in CVDs prevention. Several studies have already showed the protective effects of natural antioxidants on EPCs levels and functionality; some examples are resveratrol, catechin and folic acid. Fermentation has recently shown interesting roles in cardiovascular prevention since this process gave origin to a new class of foods, rich in bioactive compounds, the fermented foods. Consumption of fermented legumes and cereals, but also fermented beverages (such as beer and wine) was found to protect endothelial function through both lipid-lowering, as well anti-inflammatory and antioxidative mechanisms. Little is known about the effects of fermentation-derived nutraceuticals on EPCs. Given the important role of this cardiovascular biomarker, further analysis in this field can improve opportunities for CVDs prevention and treatment. Vascular endothelium and EPCs: new insightsFor many years vascular endothelium has been considered a mere physical barrier between blood and underlying tissues; recent studies have demonstrated new and interesting roles of endothelium in vascular health [1] .Endothelial cells composing this monolayer have therefore paracrine, endocrine and autocrine functions, by secreting several factors with vasodilatory and antiproliferative effects, such as endothelium-derived hyperpolarization factor (EDHF), nitric oxide (NO) and prostacyclin (PGI 2 ), and others inducing vasoconstrictor response, for instance endothelin-1 (ET-1), angiotensin II and reactive oxygen species (ROS) [2] . These evidences make the vascular endothelium a multifunctional unit that regulates vascular homeostasis by REVIEW

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“…Id1 is a regulator of cellular proliferation and differentiation with its expression dysregulated in EPCs during disease [86]. For example, EPCs isolated from type-1 diabetic patients and patients with ovarian cancer have elevated expression of Id1 compared to healthy controls [87][88][89]. Moreover, in ovarian cancer this increase in Id1 has been linked with increased levels of integrin 4 (Table 1) and PI3K/Akt-induced EPC mobilisation, recruitment, and survival, likely contributors to the progression of the cancer [88,90].…”

Section: Inhibitor Of Dna-bindingmentioning

confidence: 99%

Regulation of EPCs: The Gateway to Blood Vessel Formation

Parham

Pitson

Bonder

2014

New Journal of Science

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Endothelial progenitor cells (EPCs) are primitive endothelial precursors which are known to functionally contribute to the pathogenesis of disease. To date a number of distinct subtypes of these cells have been described, with differing maturation status, cellular phenotype, and function. Although there is much debate on which subtype constitutes the true EPC population, all subtypes have endothelial characteristics and contribute to neovascularisation. Vasculogenesis, the process by which EPCs contribute to blood vessel formation, can be dysregulated in disease with overabundant vasculogenesis in the context of solid tumours, leading to tumour growth and metastasis, and conversely insufficient vasculogenesis can be present in an ischemic environment. Importantly, it is widely known that transcription factors tightly regulate cellular phenotype and function by controlling the expression of particular target genes and in turn regulating specific signalling pathways. This suggests that transcriptional regulators may be potential therapeutic targets to control EPC function. Herein, we discuss the observed EPC subtypes described in the literature and review recent studies describing the role of a number of transcriptional families in the regulation of EPC phenotype and function in normal and pathological conditions.

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Folic acid supplementation normalizes the endothelial progenitor cell transcriptome of patients with type 1 diabetes: a case-control pilot study

Cited by 39 publications

References 65 publications

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus

Nutraceuticals and cardiovascular risk: potential role of EPCs modulation

Regulation of EPCs: The Gateway to Blood Vessel Formation

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